Trifluoroacetic acid → HCID 57998014, compound

Participants

Reaction Steps

To an iced slurry of (2S,4R)-methyl 4-(biphenyl-4-yl)-4-(methylthio)pyrrolidine-2-carboxylate, TFA (174 mg, 0.394 mmol), (S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoic acid (100 mg, 0.434 mmol), and HATU (225 mg, 0.591 mmol) in DCM (5 mL) was added N,N-Diisopropylethylamine (0.207 mL, 1.182 mmol). The formed colorless slurry was stirred at room temperature overnight. Diluted with DCM, quenched with 5% citric acid. The organic layer was washed with 0.1 M NaOH and brine, dried over MgSO4, filtered, evaporated in vacuo. The residue was purified by BIOTAGE® column, eluted with 5˜35% etOAc-hexane to yield the desired product (2S,4R)-methyl 4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(methylthio)pyrrolidine-2-carboxylate (178 mg, 0.296 mmol, 75% yield) as a white solid. 1H NMR (500 MHz, MeOD) ppm 1.12 (s, 9H), 1.46 (s, 9H), 1.86 (s, 3H), 2.60 (dd, J=12.97, 6.87 Hz, 1H), 2.90 (dd, J=12.82, 7.93 Hz, 1H), 3.74 (s, 3H), 4.11 (d, J=11.29 Hz, 1H), 4.35-4.48 (m, 2H), 4.73 (d, J=10.99 Hz, 1H), 7.36 (t, J=7.02 Hz, 1H), 7.42-7.51 (m, 3H), 7.54-7.71 (m, 5H). LC-MS (retention time: 3.34 min, method B), MS m/z 541 (M+H).

Provenance & Evidence