Methanol → Methyl cis(+/-)1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4-[3-(6-methoxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 4-[3-(6-methoxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate (Intermediate 220) (150 mg, 0.414 mmol) in ethanol (2 mL) was treated with K2CO3 (63 mg, 0.455 mmol) followed by a solution of 2-[(1E)-3-chloroprop-1-en-1-yl]-1,4-difluorobenzene (Intermediate 124) (86 mg, 0.455 mmol) in ethanol (1 mL). The reaction was warmed to 40° C. for 18 hours. The reaction was partitioned between ethyl acetate and water. The aqueous layer was extracted with dichloromethane (2×20 mL). The organic extracts were combined, dried over MgSO4 and concentrated at reduced pressure to obtain a yellow oil. Chromatography on silica gel eluting with (0-2.5%) methanol in dichloromethane gave the title compound as a yellow oil (120 mg, 56%).

Provenance & Evidence