Acetic Acid → HCID 18972703, compound

Participants

Reaction Steps

A dioxane solution of (+/-) 6-chloro-4-ethynyl-4-(1,1,1-trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one (150 mg, 0.544 mmol), pyrrolidine (52.2 gL, 0.626 mmol), paraformaldehyde (20.5 mg, 0.681 mmol), acetic acid (31.1 gL, 0.544 mmol) and copper (I) chloride (20.5 mg, 0.207 mmol in 3.5 ml dioxane) was heated to 50° C. in an oil bath for approximately 2 h. The reaction mixture was quenched into 2N HCl and extracted with ethyl acetate. The aqueous layer was neutralized with solid potassium carbonate and extracted with ethyl acetate (3x). The combined extracts were washed with water and brine before drying over sodium sulfate to afford 140 mg crude product. Chromatographic purification on silica gel and recrystallization from ethyl acetate: hexane afforded crystalline (+/-) 6-chloro-4-(1,1,1-trifluoromethyl)-4-[(3-(1-pyrrolidinyl))-1-propynyl]-1,4-dihydro-2H-3,1-benzoxazin-2-one (89 mg, 46% yield): MP 160°-161° C. (dec). 1H-NMR (CDCl3): δ1.85-1.89 (m, 4H), 2.68-2.71 (m, 4H), 3.67 (s, 1H), 6.88 (d, J=8.55 Hz, 1H), 7.40 (dd, J=2.19, 8.54 Hz, 1H), 7.55 (s, 1H), 9.45 (s, 1H).

Provenance & Evidence