Trifluoroacetic acid → HCID 90026716, compound

Participants

Reaction Steps

N,N-Diisopropylethylamine (900 mg, 1.22 ml, 6.97 mmol, Eq: 2.00) was added to 3,3-difluoropyrrolidine hydrochloride (500 mg, 3.5 mmol, Eq: 1.00) in diethyl ether (10 ml). A solution of cyanic bromide (369 mg, 3.5 mmol, Eq: 1.00) in diethyl ether (2 mL) was added at 0° C. The mixture was stirred over night at room temperature, filtered and concentrated on a rotatory evaporator at 40° C., keeping the pressure above 100 mbar (product is volatile). 2,2-Dichloroacetyl chloride (510 mg, 0.336 ml, 3.5 mmol, Eq: 1.00) was added to the crude intermediate at 0° C. The mixture was stirred for 15 min. Dichloromethane (6 ml) was added, followed by N,N-diisopropylethylamine (452 mg, 0.61 ml, 3.5 mmol, Eq: 1.00). tert-Butyl 1-methylhydrazinecarboxylate (555 mg, 0.62 ml, 3.8 mmol, Eq: 1.09) was added dropwise at 0° C. The reaction mixture was stirred for 1 h at room temperature. Trifluoroacetic acid (4 g, 2.7 ml, 35 mmol, Eq: 10) was added. The reaction mixture was heated under refluxed for 1.5 h and then concentrated to an oil. The mixture was partitioned between a saturated sodium bicarbonate solution and ethyl acetate. The combined organic layers were washed with a saturated ammonium chloride solution and then dried over sodium sulfate and concentrated to an oil. Ethanol (12 ml) and water (24 ml) were added, followed by sodium acetate (717 m g, 8.75 mmol, Eq: 2.5). The reaction mixture was heated to 60° C. for 1 h. The mixture was extracted with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give the desired product (699 mg, 92%) as a white powder. MS: m/z=217.3 (M+H+)

Provenance & Evidence