7084-93-7

Usage

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

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

Downstream Products

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

Relevant academic research and scientific papers

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.

Polysilane-Immobilized Rh-Pt Bimetallic Nanoparticles as Powerful Arene Hydrogenation Catalysts: Synthesis, Reactions under Batch and Flow Conditions and Reaction Mechanism

Hydrogenation of arenes is an important reaction not only for hydrogen storage and transport but also for the synthesis of functional molecules such as pharmaceuticals and biologically active compounds. Here, we describe the development of heterogeneous Rh-Pt bimetallic nanoparticle catalysts for the hydrogenation of arenes with inexpensive polysilane as support. The catalysts could be used in both batch and continuous-flow systems with high performance under mild conditions and showed wide substrate generality. In the continuous-flow system, the product could be obtained by simply passing the substrate and 1 atm H2 through a column packed with the catalyst. Remarkably, much higher catalytic performance was observed in the flow system than in the batch system, and extremely strong durability under continuous-flow conditions was demonstrated (>50 days continuous run; turnover number >3.4 × 105). Furthermore, details of the reaction mechanisms and the origin of different kinetics in batch and flow were studied, and the obtained knowledge was applied to develop completely selective arene hydrogenation of compounds containing two aromatic rings toward the synthesis of an active pharmaceutical ingredient.

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.

N-(Cyclohexylcarbonyl)-D-phenylalanines and related compounds. A new class of oral hypoglycemic agents. 2

A series of analogues of N-(cyclohexylcarbonyl)-D-phenylalanine (5) have been synthesized and evaluated for their hypoglycemic activity. Relationships were studied between the activity and the three-dimensional structure of the acyl moiety, which was characterized by high-resolution 1H NMR spectroscopy and MNDO calculations. The role of the carboxyl group of the phenylalanine moiety was also studied by comparing the activities of the enantiomers, the decarboxyl derivative, the esters, and the amides of the phenylalanine derivatives. Thus, the structural requirements for possessing hypoglycemic activity was elucidated and a highly active compound, N-[(trans-4-isopropylcyclohexyl)carbonyl]-D-phenylalanine (13) was obtained, which showed a 20% blood glucose decrease at an oral dose of 1.6 mg/kg in fasted normal mice.