Trifluoroacetic acid → 4-(2,5-difluorophenyl)-2-(3-hydroxyphenyl)-N,N-dimethyl-2,5-dihydro-1H-pyrrole-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-4-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate (3-2, 1.48 g, 3.82 mmol) was dissolved in anhydrous CH2Cl2 (25 mL) and treated with TFA (5 mL) for 1 hour. The reaction mixture was partitioned between sat. aq. NaHCO3 (100 mL) and ethyl acetate (3×20 mL). The combined organic layers were then washed with sat. aqueous NaCl, dried over sodium sulfate, filtered, and concentrated. The crude amine was then dissolved in CH2Cl2, and treated successively with Et3N (1.6 mL, 11.5 mmol) and dimethylcarbamoyl chloride (0.37 mL, 4.01 mmol), and the resulting solution was stirred 3.5 h at 25° C. Upon completion as judged by mass spectrometry, the reaction was concentrated, redissolved in CH2Cl2 (30 mL) and triethylamine trihydrofluroide complex (0.6 mL, 3.82 mmol) was added and the reaction stirred an additional 12 h at 25° C. Upon completion, the reaction was partitioned between NH4Cl (10 mL) and CH2Cl2 (3×10 mL), and the combined organic layers were concentrated. The desired compound crystallized from CH2Cl2 and as filtered to provide 4-(2,5-difluorophenyl)-2-(3-hydroxyphenyl)-N,N-dimethyl-2,5-dihydro-1H-pyrrole-1-carboxamide 4-1 as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.18 (t, J=7.8 Hz, 2H), 7.00 (m, 3H), 6.90 (s, 1H), 6.84 (d, J=7.7 Hz, 1H), 6.74 (dd, J=7.9, 2.4 Hz, 1H), 4.90 (dd, J=13.4, 3.7 Hz, 1H), 4.50 (d, J=13.4 Hz, 1H), 2.91 (s, 6H). LRMS: m/z (M−CH3) 345.3 found, 345.4 required.

Provenance & Evidence