Back to results
US 2026/0258454 A1Published application
Biocatalytic synthesis of (1s,3s)-3-hydroxycyclohexane-1-carboxylic acid compounds
AssigneeBristol-Myers Squibb Company
InventorsShane McKenna, Yichen Tan, Michael J. Smith, Richard J. Fox, David Thomas George, Candice Lee Joe
Life of this patent
Estimating the term…
Abstract
Improved methods and intermediates thereof for preparing (1S,3S)-3-hydroxycyclohexane-1-carboxylic acid are described. These compounds are useful as intermediates for making carbamoyloxymethyl triazole cyclohexyl acid LPA antagonists.
Claims9
A method of making a compound of Formula (I):
- comprising (1) contacting a compound of Formula (II) thereof:
- with a halogenating reagent or a sulfonylating reagent in a polar aprotic solvent or solvent mixture, with or without an inorganic or organic base;
- for a time and at a temperature sufficient for deoxy-functionalization to produce a compound of Formula (III):
- wherein R is Cl, Br, I, OMs, OTs, or OTf;
- (2) with or without isolating the compound of Formula (III), contacting the compound of Formula (III) with a palladium catalyst, with or without a phosphine ligand, and an inorganic or organic base, in water and a polar aprotic solvent;
- purged with carbon monoxide;
- for a time, at a temperature and pressure sufficient for carbonylation to produce the compound of Formula (I).
4 more elements
A method of making a compound of Formula (IV):
- comprising contacting a compound of Formula (I) thereof:
- with an enone reductase enzyme (ERED) and a ketoreductase enzyme (KRED), in the presence of an aqueous polar protic solvent, NADPH and a co-substrate, with or without an organic cosolvent;
- for a time and at a temperature sufficient to produce the compound of Formula (IV).
8-10. (canceled)
A method of making a compound of Formula (IV):
- comprising (1) contacting a compound of Formula (II):
- with oxalyl chloride in a mixture of 2-MeTHF and DMF;
- for 1 to 3 hours and at 0 to 50° C. to produce a compound of Formula (IIIa):
- (2) with or without isolating the compound of Formula (IIIa), contacting the compound of Formula (IIIa) with Pd(A-taPhos)2Cl2 and Na2CO3, in water and 2-MeTHF;
- purged with carbon monoxide;
- for 16 to 20 hours, at 20-50° C. and 30 to 35 psi to produce the compound of Formula (I):
- then (3) contacting a compound of Formula (I) with ERED-310, and KRED 457, in the presence of an aqueous buffer selected from phosphate, TRIS, HEPES, ACES, BES, MOPS, and Tricene;
- GDH, NADPH and glucose with or without an organic cosolvent such as DMSO, IPA, dioxane or acetone;
- for at least 16 hours and at 25 to 35° C. sufficient to produce the compound of Formula (IV).
6 more elements
Dependencies are inferred from the claim text.