Thiazole → HCID 70983650, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled solution of iPrMgCl—LiCl (1.3 M in THF, 187 mL, 243 mmol) at −5° C. was added thiazole (17.4 mL, 243 mmol) at such a rate that the internal temperature did not exceed 5° C. The resulting slurry was warmed to 15° C. over 15 minutes, and then cooled to −10° C. To the reaction mixture was added ethyl 4-formyl-2-methylcyclohexanecarboxylate (41 g, 207 mmol) as a solution in THF (100 mL) at such a rate the internal temperature did not exceed 5° C. The reaction mixture was stirred for 30 minutes at 0° C., and then quenched with water (100 mL) and diluted with EtOAc (500 mL) and 1N HCl (500 mL). The organic layer was separated, and the aqueous layer extracted again with EtOAc (700 mL). The organic layers were combined, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was diluted with DCM (500 mL), and to this mixture was added Dess-Martin periodinane (88 g, 208 mmol). During the addition, the temperature was controlled such that the internal temperature did not exceed 35° C. After 1 hour, the reaction mixture was cooled to room temperature and then diluted with saturated aqueous NaHCO3 (600 mL), aqueous 5% sodium sulfite (600 mL), and dichloromethane (600 mL). The heterogeneous mixture was stirred until both layers were clear. The layers were separated and the aqueous layer was extracted a second time with dichloromethane (600 mL). The organic layers were combined, dried over MgSO4, filtered, absorbed on silica, and purified by silica gel chromatography to afford ethyl 2-methyl-4-(1,3-thiazol-2-ylcarbonyl)cyclohexanecarboxylate. MS ESI calc'd. for C14H20NO3S [M+H]+ 282. found 282.

Provenance & Evidence