7084-93-7

Basic information

• Product Name: cis-4-isopropylcyclohexanecarboxylic acid
• Synonyms: cis-4-isopropylcyclohexanecarboxylic acid;(1α)-4α-Isopropylcyclohexanecarboxylic acid;4α-Isopropylcyclohexane-1α-carboxylic acid
• CAS NO: 7084-93-7
• Molecular Formula: C₁₀H₁₈O₂
• Molecular Weight: 170.24872
• EINECS: 230-385-2
• Mol File: 7084-93-7.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 263.8°C at 760 mmHg
• Flash Point: 126.9°C
• Appearance: /Solid
• Density: 0.996g/cm³
• Vapor Pressure: 0.00294mmHg at 25°C
• Refractive Index: 1.469
• CAS DataBase Reference: cis-4-isopropylcyclohexanecarboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: cis-4-isopropylcyclohexanecarboxylic acid(7084-93-7)
• EPA Substance Registry System: cis-4-isopropylcyclohexanecarboxylic acid(7084-93-7)

Safety Data

• TSCA: Yes
• Hazardous Substances Data: 7084-93-7(Hazardous Substances Data)

Usage

Description

cis-4-Isopropylcyclohexanecarboxylic acid is an organic compound that is the cis-isomer of trans-4-Isopropylcyclohexanecarboxylic acid. It is characterized by its unique molecular structure, which consists of a cyclohexane ring with an isopropyl group and a carboxylic acid group attached to the fourth carbon atom. cis-4-isopropylcyclohexanecarboxylic acid is known for its potential applications in the pharmaceutical industry.

Uses

Used in Pharmaceutical Industry:
cis-4-Isopropylcyclohexanecarboxylic acid is used as an intermediate in the synthesis of Nateglinide (N379375), a novel D-phenylalanine-derivative hypoglycemic agent. cis-4-isopropylcyclohexanecarboxylic acid plays a crucial role in the preparation process, contributing to the development of medications for the treatment of diabetes and related conditions.
cis-4-Isopropylcyclohexanecarboxylic acid is used as a key component in the production of Nateglinide for its hypoglycemic properties, helping to regulate blood sugar levels in patients with diabetes.

InChI:InChI=1/C10H18O2/c1-7(2)8-3-5-9(6-4-8)10(11)12/h7-9H,3-6H2,1-2H3,(H,11,12)/t8-,9+

Synthetic route

Methyl cis-4-isopropylcyclohexanecarboxylate (13828-35-8) → (1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7)

Conditions	Yield
With sodium hydroxide In methanol for 0.166667h; Ambient temperature;	64%

4-Isopropylbenzoic acid (536-66-3) → trans-4-isopropylcyclohexane-1-carboxylic acid (7077-05-6) + (1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7)

Conditions	Yield
With sodium hydroxide; nickel at 195℃; under 73550.8 Torr; Hydrogenation;
With sodium hydroxide; nickel at 200℃; under 110326 - 147102 Torr; Hydrogenation;
With acetic acid; platinum Hydrogenation;
With hydrogen at 80℃; under 7600.51 Torr; for 36h; Autoclave; Overall yield = 87 %; Overall yield = 148.1 mg;	A n/a B n/a

p-menthan-7-oic acid methyl ester (175284-00-1) → trans-4-isopropylcyclohexane-1-carboxylic acid (7077-05-6) + (1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7)

Conditions	Yield
With sodium hydroxide; sodium hydride 1) 150 deg C, 2 h, 2) MeOH, 20 deg C, 10 min; Yield given. Multistep reaction;
With sodium phosphate buffer; lipase from Candida rugosa for 6.5h; pH 7.2; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(S)-p-menthen-(1)-oic acid (7) → (1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7)

Conditions	Yield
With acetic acid; platinum Hydrogenation;

(4S)-phellandric acid (135355-08-7) + acetic acid (64-19-7) + platinum → (1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7)

Conditions	Yield
Hydrogenation;

4-Isopropylbenzoic acid (536-66-3) → (1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) H2, 2) SOCl2 / 1) PtO2 / 1) 5 kg/cm2, r.t., 2 h 2: 64 percent / 2N aq. NaOH / methanol / 0.17 h / Ambient temperature View Scheme

(1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7) + 3-(5-amino-2-methylphenyl)-7-((3-amino-4-methylphenyl)-amino)-1-methyl-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one → N-(3-(7-(3-amino-4-methylphenylamino)-1-methyl-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)-4-methylphenyl)-4-isopropylcyclohexanecarboxamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 14h; Inert atmosphere;	48%

ethanol (64-17-5) + (1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7) → trans-p-menthanoic acid-(7)-ethyl ester (25244-24-0, 92037-39-3) + cis-p-menthanoic acid-(7)-ethyl ester (25244-24-0)

Conditions	Yield
With sulfuric acid

(1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7) → cis-p-menthanoic acid-(7)-(4-bromo-phenacyl ester) (107628-01-3)

(1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7) → cis-p-menthanoic acid-(7)-(4-chloro-phenacyl ester)

(1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7) + D-phenylalanine methyl ester (21685-51-8) → N-<(cis-4-Isopropylcyclohexyl)carbonyl>-D-phenylalanine methyl ester (958230-60-9)

Conditions	Yield
With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide 1) CHCl3, 3 h, 2) CHCl3, 25 deg C, 1 d; Multistep reaction;

(1r,4s)-4-isopropylcyclohexanecarboxylic acid (7084-93-7) → N-[(cis-4-Isopropylcyclohexyl)carbonyl]-D-phenylalanine

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) N-hydroxysuccinimide, dicyclohexylcarbodiimide / 1) CHCl3, 3 h, 2) CHCl3, 25 deg C, 1 d 2: 2N NaOH / methanol View Scheme

Upstream product

• 13828-35-8 Methyl cis-4-isopropylcyclohexanecarboxylate 
• 175284-00-1 p-menthan-7-oic acid methyl ester 
• 536-66-3 p-isopropylbenzoic acid 
• 135355-08-7 (4S)-phellandric acid 
• 64-19-7 acetic acid 

Downstream Products

• 25244-24-0 trans-p-menthanoic acid-⁽⁷⁾-ethyl ester 
• 25244-24-0 cis-p-menthanoic acid-⁽⁷⁾-ethyl ester 
• 107628-01-3 cis-p-menthanoic acid-⁽⁷⁾-(4-bromo-phenacyl ester) 
• 105816-05-5 N-[(cis-4-Isopropylcyclohexyl)carbonyl]-D-phenylalanine 
• 958230-60-9 N-<(cis-4-Isopropylcyclohexyl)carbonyl>-D-phenylalanine methyl ester 

Relevant articles and documents

Electrocatalytic hydrogenation of benzoic acids in a proton-exchange membrane reactor

The highly efficient chemoselective electrocatalytic hydrogenation of benzoic acids (BAs) to cyclohexanecarboxylic acids (CCAs) was carried out in a proton-exchange membrane reactor under mild conditions without hydrogenation of the carboxyl group. Among the investigated catalysts, the PtRu alloy catalyst was found to be the most suitable for achieving high current efficiencies for production of CCAs. An electrochemical spillover mechanism on the PtRu alloy catalyst was also proposed.

Separation of cis/trans-cyclohexanecarboxylates by enzymatic hydrolysis: Preference for diequatorial isomers

4-Substituted cis/trans-cyclohexanecarboxylates have been separated into the isomers by enzymatic hydrolysis with lipase from Candida rugosa with very good selectivity. The enzyme preferentially recognizes diequatorial conformations. Copyright (C) 1996 Elsevier Science Ltd.