Thiazole → HCID 178451153, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled (0° C.) flask under nitrogen containing iPrMgCl—LiCl (1.3 M in THF, 55.2 mL, 71.8 mmol) was added thiazole (5.10 mL, 71.8 mmol) keeping the internal temperature <10° C. The resulting heterogenous mixture was warmed to RT where it was stirred for 10 min then re-cooled to −20° C. Then, a solution of butyl trans-4-acetylcyclohexanecarboxylate (12.5 g, 55.2 mmol) in THF (20+5 mL) was added via syringe. The cooling bath was then removed and the reaction mixture warmed slowly to 10° C. during which time it was observed to nearly completely homogenize. After 40 min, saturated aqueous NH4Cl followed by EtOAc were added and the layers separated, the organics dried over MgSO4, filtered and concentrated in vacuo. The crude residue was absorbed on silica and purified by flash chromatography to afford butyl trans-4-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]cyclohexanecarboxylate as a light yellow oil. The enantiomers were separated by chiral SFC (Chiral Technology AZ-H, 2.1×25 cm, 5 uM, 45/55 MeOH/CO2, Flow Rate: 80 mL/min, 6 min run time, WL: 220 nm) Elution was observed at 2.98 min and 4.14 min. Pooled fractions of each peak were separately concentrated under reduced pressure.

Provenance & Evidence