tert-Butyl 4-carbamothioylpiperidine-1-carboxylate → 4‐{4‐[5‐(2,6‐Difluorophenyl)‐4,5‐dihydro‐1,2‐ oxazol‐3‐yl]‐1,3‐thiazol‐2‐yl}piperidine

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-tert-butoxycarbonylpiperidine-4-carbothioamide (7.33 g, 30 mmol) and 2-bromo-1-(4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl)ethanone (i.e. the product of Step C) (9.12 g, 30 mmol) in acetone (100 mL) was heated at 45° C. for 3 h, and then stirred at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was dissolved in dichloromethane (100 mL) and trifluoroacetic acid (40 mL), stirred at room temperature for 3 h and then concentrated under reduced pressure. The resulting oil was dissolved in aqueous hydrochloric acid solution (0.5 N, 200 mL) and extracted with ethyl acetate. The organic layer was basified by adding aqueous sodium hydroxide solution (10% in water), then washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound as a thick amber-colored oil (8.62 g, weight included residual ethyl acetate).

Provenance & Evidence