4-(chloromethyl)-1-cyclopentyl 2-(trifluoromethyl)benzene (957208-65-0 ) Manufacturer Supplier Exporter Mediocon Inc.
4-(chloromethyl)-1-cyclopentyl 2-(trifluoromethyl)benzene (957208-65-0 ) Manufacturer Supplier Exporter
Mediocon Inc.
Name: 4-(chloromethyl)-1-cyclopentyl
2-(trifluoromethyl)benzene
CAS No: 957208-65-0
Molecular Weight: 262.69g/mol
Molecular formula
: C₁₃H₁₄ClF₃
Synonyms- 1-Cyclopentyl-4-(chloromethyl)-2-(trifluoromethyl)benzene
4-(Chloromethyl)-1-cyclopentyl-2-(trifluoromethyl)benzene
Benzene, 1-(chloromethyl)-4-cyclopentyl-2-(trifluoromethyl)-
2-Trifluoromethyl-4-chloromethyl-1-cyclopentylbenzene Appearance: colorless to light-yellow liquid or oil.
Solubility : soluble in organic solvents.
Use :
4-(Chloromethyl)-1-cyclopentyl-2-(trifluoromethyl)benzene (CAS No.
957208-65-0) is a specialized organic building block primarily used in
high-end pharmaceutical research and synthesis. Its value lies in its unique
arrangement of functional groups, which allows it to serve as a key
intermediate for complex drug molecules.
Primary Use: Pharmaceutical
Intermediate
The most significant application of this compound is as a precursor for Etrasimod
(also known as APD334). Etrasimod is a selective S1P1 receptor modulator
used to treat autoimmune and inflammatory conditions, such as:
- Ulcerative
Colitis: It helps regulate the movement of lymphocytes
(white blood cells), preventing them from reaching and damaging the
intestinal lining.
- Other
Autoimmune Disorders: It is investigated
for various conditions requiring immune system modulation, including
Crohn’s disease and atopic dermatitis.
Chemical Characteristics
& Reactivity
The molecule is highly versatile for chemists because it contains three
distinct "handles" for further reactions:
|
Feature |
Chemical
Role |
Impact |
|
Chloromethyl
Group ($–CH_2Cl$) |
Alkylating
Agent |
Allows
for nucleophilic substitution reactions (e.g., adding amines, ethers, or
thiols) to build the core structure of a drug. |
|
Trifluoromethyl
Group ($–CF_3$) |
Metabolic
Stabilizer |
Enhances
the drug's lipophilicity (fat-solubility) and prevents the body from breaking
the molecule down too quickly. |
|
Cyclopentyl
Group |
Hydrophobic
Tail |
Provides
structural bulk and aids in the molecule's ability to fit into specific
biological receptor pockets. |
Other Research Applications
Beyond its role in Etrasimod synthesis, the compound is utilized in:
- Medicinal
Chemistry Research: As a building block
for novel drugs targeting central nervous system (CNS) disorders.
- Agrochemical
Development: Investigated as a structural scaffold for
new, high-potency pesticides or herbicides.
- Materials
Science: Used in the development of advanced materials
with specific electronic properties due to its highly fluorinated nature.
How is 4-(chloromethyl)-1-cyclopentyl
2-(trifluoromethyl)benzene manufactured by Mediocon
Inc.Synthesized?
While specific proprietary protocols for companies like Mediocon
Inc. (which appears to be a regional or specialized manufacturer) are often
not publicly disclosed in detail, the synthesis of 4-(chloromethyl)-1-cyclopentyl-2-(trifluoromethyl)benzene
(CAS 957208-65-0) follows a well-established industrial pathway.
This compound is a crucial
intermediate for the drug Etrasimod (APD334).1 Below is the standard high-yield, scalable synthetic route used by
pharmaceutical manufacturers to produce this specific building block.
Standard
Industrial Synthesis Route
The synthesis is typically a two-step
scalable process designed to minimize hazardous byproducts and maximize
regioselectivity (ensuring the groups attach to the correct carbon atoms).2
Step 1: Aryl-Alkyl Cross-Coupling
(Cyclopentylation)
The first goal is to attach the cyclopentyl
ring to the trifluoromethylbenzene core.3
· Starting Material: 1-Bromo-2-(trifluoromethyl)benzene.4
· Reagents:
Cyclopentylmagnesium bromide (a Grignard reagent).5
· Catalyst:
Typically an Iron(III) chloride (6$FeCl_3$) or Nickel (7$NiCl_2(dppp)$) catalyst.8
· Reaction: The
Grignard reagent reacts with the brominated benzene in a cross-coupling
reaction to form 1-cyclopentyl-2-(trifluoromethyl)benzene.9
· Conditions:
Temperature is strictly controlled (often starting at 10$-65$°C and warming to room temperature) to prevent side reactions like
Wagner-Meerwein rearrangements.11
Step 2: Regioselective
Chloromethylation
The final step adds the chloromethyl "handle" ($–CH_2Cl$) to the 4-position of the ring.
· Intermediate:
1-Cyclopentyl-2-(trifluoromethyl)benzene.12
· Chloromethylating Agents: A mixture of Trioxane (a source
of formaldehyde) and Thionyl chloride (13$SOCl_2$) or chlorosulfonic acid.14
· Catalyst/Solvent: Sulfuric acid (15$H_2SO_4$) in
Dichloromethane (DCM).16
· Mechanism:
The trifluoromethyl group (17$–CF_3$) is
strongly electron-withdrawing, which directs the incoming chloromethyl group to
the para position relative to the cyclopentyl group.18
· Result: This
yields the final product with high purity (often 19$>98\%$ regioselectivity).20
Manufacturing
Advantages
Manufacturers like Mediocon likely employ these methods
because:
1.
Safety: Using trioxane/thionyl chloride avoids the direct use of highly
carcinogenic chloromethyl methyl ether (BCME).
2.
Scalability: The reactions are exothermic but manageable in large-scale jacketed
reactors.
3.
Cost: The starting materials (substituted
benzenes and cyclopentyl halides) are commercially available and relatively
inexpensive.21
Quality Control Specifications
In an industrial setting, the final product is typically
tested for:
· Purity: 22$>96\%$ by HPLC/GC.23
· Identity: Confirmed via $^1H$ NMR and MS.
· Appearance:
Colorless to light yellow/brown liquid.24
What are the effects And Side effects of 4-(chloromethyl)-1-cyclopentyl
2-(trifluoromethyl)benzene Manufactured
by Mediocon Inc. LTD.?
The compound (3S)-3-[4-[(2-chloro-5-iodophenyl)methyl]phenoxy]tetrahydrofuran
(CAS: 915095-94-2) is a specialized chemical produced by companies like Mediocon
Inc. Primarily, it is used as a pharmaceutical
intermediate, not as a final medication.
Because it is an intermediate and not a finished drug
prescribed to patients, it does not have "side effects" in the
medical sense (like a headache or nausea). Instead, its "effects" are
biological and chemical properties observed in a laboratory setting.
1. Primary
Use: Synthesis of Empagliflozin
This compound is a key building
block for the synthesis of Empagliflozin (Jardiance), a popular
medication for Type 2 Diabetes and Heart Failure.
· Biological Target: It is designed to
eventually form part of a molecule that inhibits SGLT2 (sodium-glucose
co-transporter 2).
· Function: By inhibiting SGLT2, the final
drug prevents the kidneys from reabsorbing glucose into the blood, causing the
excess sugar to be removed through urine.
2. Emerging Research: Anticancer
Activity
Scientific studies (such as those published in Medicinal
Chemistry Research) have investigated this specific compound (and its
halogenated analogs) for other uses:
· Microtubule Destabilizing Agent: Research suggests it may act as an anticancer agent by interfering
with the structural components (microtubules) that cancer cells need to divide
and grow.
· Anti-inflammatory Potential: It has been
explored as a ligand in receptor-binding studies to evaluate its ability to
reduce inflammation.
3. "Side Effects"
(Safety & Handling Hazards)
In the context of a manufacturing company like Mediocon
Inc., the "side effects" refer to toxicological hazards for
researchers and workers handling the chemical:
· Skin & Eye Irritation: As a
halogenated aromatic compound, it is likely a skin and eye irritant.
· Respiratory Risk: Inhalation of the fine
powder or vapors can irritate the respiratory tract.
· Persistence: Due to the chlorine and
iodine atoms, these types of molecules are often stable and may be persistent
in the environment if not disposed of correctly.
How is 4-(chloromethyl)-1-cyclopentyl 2-(trifluoromethyl)benzene Manufactured
by Mediocon Inc. Tested Qualitatively?
Qualitative testing (or "identification") is the
process used to confirm that a chemical batch is indeed 4-(chloromethyl)-1-cyclopentyl-2-(trifluoromethyl)benzene
and that it meets the structural requirements for use as an intermediate.
Based on standard pharmaceutical manufacturing practices
for this specific compound (CAS 957208-65-0), manufacturers like Mediocon
Inc. utilize a combination of spectroscopic and chromatographic techniques
to ensure identity and purity.
1. Primary Identification:
Nuclear Magnetic Resonance (NMR)
NMR is the most critical qualitative test for this compound
because it confirms that the three functional groups are attached to the
benzene ring in the correct relative positions.
· $1H$ NMR (Proton NMR): Used to identify the
distinctive "chemical fingerprints."
o
Chloromethyl group ($–CH_2Cl$): Appears as a
sharp singlet at approximately $\delta$
4.5–4.6 ppm.
o
Cyclopentyl ring: Multiple signals (multiplets) between $\delta$
1.5–3.2 ppm.
o
Aromatic Protons: Two distinct doublets around $\delta$
7.4–7.6 ppm, confirming the para-substitution pattern relative to
the other groups.
· $^{19}F$ NMR (Fluorine NMR): Specifically
confirms the presence of the Trifluoromethyl ($-CF_3$)
group, which appears as a characteristic singlet, usually around $-60$ to $-63$
ppm.
2. Purity Assessment: HPLC and GC
While identification confirms "what" the
substance is, these tests confirm how "clean" it is.
· HPLC (High-Performance Liquid Chromatography): Used to check for related substances and isomers. Manufacturers
typically use a C18 column with an acetonitrile/water mobile phase.
· GC (Gas Chromatography): Since this
compound is an oil/liquid and relatively volatile, GC is often used to detect
residual solvents (like Dichloromethane or THF) used during the manufacturing
process.
3. Mass Spectrometry (MS)
MS is used to confirm the Molecular Weight ($262.70$ g/mol).
· Isotopic Pattern: Because the molecule
contains a Chlorine atom, the mass spectrum will show two distinct peaks (M and
M+2) in a 3:1 ratio, which is a definitive qualitative indicator for
chlorinated compounds.
4. Physical Characterization
Qualitative testing also includes simple physical checks to
ensure the batch matches the "Reference Standard":
· Appearance: Must be a colorless to light-yellow
oily liquid.
· Solubility: Must be fully soluble in
organic solvents like DMSO, Chloroform, or Methanol.
· FT-IR (Infrared Spectroscopy): Used to
identify functional group vibrations, specifically the $C–F$
stretching bonds and the aromatic ring vibrations.
Which tests are performed on 4-(chloromethyl)-1-cyclopentyl
2-(trifluoromethyl)benzene Manufactured
Mediocon Inc. LTD.?
For a high-purity pharmaceutical intermediate like 4-(chloromethyl)-1-cyclopentyl-2-(trifluoromethyl)benzene
(CAS: 957208-65-0), manufacturers like Mediocon Inc. LTD. perform a
rigorous battery of tests to ensure the material meets "Pharmacy
Grade" or "Research Grade" specifications (typically $>98\%$ or $>99\%$
purity).
The testing is divided into Identity, Purity,
and Physical Characteristic checks.
1. Identity & Structural
Confirmation
These tests prove the molecule is exactly what it claims to
be, with all groups in the correct positions.
· $1H$ NMR Spectroscopy (Proton NMR): The
"gold standard" for structural verification. Specifically, it looks
for the chloromethyl singlet at ~4.5 ppm and the cyclopentyl
multiplets between 1.5–3.2 ppm.
· $^{19}F$ NMR Spectroscopy (Fluorine NMR): Since
the molecule contains a trifluoromethyl ($-CF_3$)
group, this test confirms its presence via a sharp singlet around $-60$ to $-63$
ppm.
· Mass Spectrometry (LC-MS / HRMS): Confirms the exact molecular weight of 262.70 g/mol.1 It also detects the characteristic 3:1 isotopic ratio of
Chlorine ($^{35}Cl$ and $^{37}Cl$),
which is a definitive identifier.
· FT-IR (Infrared Spectroscopy): Used to
identify the "functional group fingerprint," specifically the $C-F$ stretching and aromatic ring vibrations.
2. Purity & Compositional
Testing
These tests measure how much of the batch is the desired
product versus impurities.
· HPLC (High-Performance Liquid Chromatography): Typically uses a C18 column (e.g., Zorbax SB-C18) with an
acetonitrile/buffer mobile phase. The goal is to ensure the "Area %"
of the main peak is $\ge 98.0\%$.
· Gas Chromatography (GC): Often used to
check for Residual Solvents. Because this chemical is synthesized using
solvents like THF or Dichloromethane, GC ensures these have been removed to
safe, trace levels.
· Water Content (Karl Fischer Titration):
Checks for moisture, as water can react with the chloromethyl group and degrade
the product over time.
3. Physical & Safety
Specification Tests
· Appearance:
Visual confirmation that the substance is a colorless to light-yellow oily
liquid.2
· Solubility Test: Confirmation that the substance dissolves completely in organic
solvents like DMSO, DCM, or Methanol.3
· Refractive Index / Density: Physical
constants (Density is approx 1.226 g/cm³) are measured to ensure
batch-to-batch consistency.
What are the challenges in Manufacturing of 4-(chloromethyl)-1-cyclopentyl
2-(trifluoromethyl)benzene Intermediate Manufactured by Mediocon Inc. LTD?
Manufacturing a high-purity pharmaceutical intermediate
like 4-(chloromethyl)-1-cyclopentyl-2-(trifluoromethyl)benzene (CAS
957208-65-0) involves several technical and safety hurdles. Companies like Mediocon
Inc. LTD must manage these challenges to ensure the material remains viable
for the synthesis of drugs like Etrasimod.
The primary manufacturing challenges are detailed below:
1. Regioselectivity and Isomer
Control
The most significant chemical challenge is ensuring the
chloromethyl group ($–CH_2Cl$) attaches
specifically to the 4-position of the benzene ring.
· The Problem: The trifluoromethyl group ($–CF_3$) and the cyclopentyl group compete to
"direct" where the next group goes. If conditions aren't perfect,
"ortho" or "meta" isomers can form.
· The Solution: Manufacturers must use a highly direct regioselective
chloromethylation (often using Trioxane and Thionyl Chloride in Sulfuric Acid)
which utilizes the electron-withdrawing nature of the 1$–CF_3$ group to favor the para position
relative to the cyclopentyl group.2
2. Low-Temperature Reaction
Control
The first step of synthesis (the
Kumada or Grignard coupling) is extremely sensitive to temperature.3
· The Challenge: Attaching the cyclopentyl
ring requires temperatures as low as $-65$°C.
· The Risk: If
the temperature rises too quickly during the addition of the Grignard reagent,
a Wagner-Meerwein rearrangement can occur.4 This changes the shape of the cyclopentyl group, rendering the
entire batch useless for pharmaceutical use.
3. Thermal Instability During
Purification
Once the crude product is created, it must be purified
(distilled) to reach the required $>98\%$
purity.
· The Challenge:
The product is thermally sensitive.5 Standard distillation at high temperatures (e.g., 6$150$°C) can cause 5–7%
loss due to decomposition.7
· The Solution: Advanced manufacturers use Wiped-Film Evaporators (WFE) or
Short-Path Distillation at lower temperatures (around 8$90$°C) and higher vacuum to protect the molecule's integrity.9
4. Handling Hazardous Reagents
The "Blanc Chloromethylation" process
traditionally used to make this compound can produce hazardous byproducts.
· Safety Risk: Older methods produced Bis(chloromethyl)
ether (BCME), a potent carcinogen.
· Industrial Mitigation: Mediocon and
similar firms use "in-situ" generation methods (like Trioxane + $SOCl_2$) that minimize the formation of BCME and
require specialized "Scrubbing" systems to neutralize acidic
byproduct gases like $HCl$ and $SO_2$.
5. Storage and Moisture
Sensitivity
The chloromethyl group is highly reactive with moisture.
· Stability Challenge: If exposed to humid
air, the chlorine atom can be replaced by a hydroxyl group, turning the product
into an alcohol.
· Logistics:
The final product must be stored under an Inert Atmosphere (Nitrogen)
and kept strictly refrigerated between 2–8°C to maintain its shelf life.10
What is the Packing for 4-(chloromethyl)-1-cyclopentyl
2-(trifluoromethyl)benzene Manufactured
by Mediocon Inc.. LTD.?
The packaging for 4-(chloromethyl)-1-cyclopentyl-2-(trifluoromethyl)benzene
(CAS No. 957208-65-0) manufactured by Mediocon Inc. LTD. (and similar
industrial suppliers) is designed to protect the chemical's stability and meet
international shipping regulations for hazardous liquids.
Because this compound is a benzyl chloride derivative,
it is highly sensitive to moisture and temperature. The packaging varies based
on the order volume.
1. Industrial/Bulk Packaging
(Large Scale)
For manufacturing and industrial use, the compound is
typically packed in bulk containers designed for chemical stability:
· Container Type: HDPE (High-Density
Polyethylene) Drums or Fiber Drums with an internal anti-static
liner.
· Standard Size: 25 kg per drum is the industrial standard for this
intermediate.
· Sealing: Double-bagged with a vacuum
seal or an Inert Atmosphere (Nitrogen flushing) to prevent the
chloromethyl group from reacting with atmospheric moisture (which would convert
it into an alcohol).
2. Lab & Research Packaging
(Small Scale)
For research and development (R&D) purposes, the
packaging is more specialized to ensure ease of handling in a lab setting:
· Container Type: Amber Glass Bottles
or Fluorinated HDPE bottles. Amber glass is used to protect the chemical
from UV light, which can trigger radical degradation.
· Standard Sizes: 1g, 5g, 10g, 25g, 100g,
500g, and 1 kg.
· Sealing: Typically secured with a Teflon-lined
screw cap and wrapped in Parafilm to ensure an airtight seal.
3. Shipping & Regulatory
Requirements
Since this chemical is classified
as a Corrosive Liquid (UN3265, Class 8, Packing Group II), the outer
packaging must comply with UN-rated safety standards:
· Secondary Containment: Bottles are
usually placed inside a secondary leak-proof container (like a sealed plastic
bag or a tin can) packed with absorbent material (vermiculite).
· Cold Chain: For long-distance transit,
it is often shipped with Ice Packs or in Refrigerated Containers
to maintain a temperature of 2–8°C.
What is shelf life Of 4-(chloromethyl)-1-cyclopentyl
2-(trifluoromethyl)benzene Manufactured by Mediocon Inc.. LTD.?
The shelf life for 4-(chloromethyl)-1-cyclopentyl-2-(trifluoromethyl)benzene
(CAS No. 957208-65-0) manufactured by Mediocon Inc. LTD. is generally
established at 2 years (24 months), provided the material is kept in its
original, unopened packaging under specific controlled conditions.
Critical Storage Parameters
Because this compound is a highly reactive benzyl chloride
derivative, its stability over that 2-year period depends entirely on strict
adherence to these storage requirements:
· Temperature:
Store at 2–8°C (refrigerated).1 While it may be stable at room temperature for short-duration
transit (shipping), long-term storage at ambient temperatures will lead to
gradual degradation.
· Atmosphere:
Keep under an Inert Atmosphere (Nitrogen or Argon blanketing).2 This prevents the chloromethyl group from reacting with oxygen or
moisture.
· Container: Must be kept in airtight,
moisture-proof containers (typically amber glass for small quantities or
HDPE drums for industrial quantities) to protect it from light and humidity.
Why Shelf Life Matters for This
Compound
The "chloromethyl" ($–CH_2Cl$)
portion of the molecule is its most reactive site. If the shelf life is
exceeded or storage is improper, the following chemical changes occur:
1.
Hydrolysis: Exposure to moisture converts the chloride into an alcohol ($–CH_2OH$), rendering it useless for further
synthesis.
2.
Polymerization/Decomposition: Over time, especially if exposed to heat or light, the molecule can
undergo self-condensation or radical reactions, reducing the HPLC purity below
the required 98–99% threshold.
Where can 4-(chloromethyl)-1-cyclopentyl
2-(trifluoromethyl)benzene Manufactured by Mediocon Inc. LTD. are procured?
4-(chloromethyl)-1-cyclopentyl 2-(trifluoromethyl)benzene Manufactured by Mediocon Inc. can be procured
from various sources, depending on your location and requirements. Here are
some options:
FOR API INTERMEDIATES
Mediocon Inc.
Plot No D 187/16 Five Star MIDC, Shendra, Aurangabad-431154, Aurangabad, Maharashtra, India
Mob/Whatsapp No: +91-9403003010, +91-9420294801
Sales Department: Email: sales@internediates.ai
Purchase Department: Email: purchase@swapnroop.com
Marketing Department: Email: mktg.sdp@gmail.com
HR Department: Email: swapnroop@gmail.com
Accounts Department: Email: swapnroop.office@gmail.com
GSTIN: 27ABGCS4218N1ZX
Mobile: 7387999183
Email: sales@intermediates.ai
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