Trifluoroacetic acid → HCID 58048576, compound

Participants

Reaction Steps

To a solution of (R)-tert-Butyl 5-((2-chlorophenyl)(1,1-dimethylethylsulfinamido)methyl)-4-methylthiazol-2-ylcarbamate, (19.0 g, 41.6 mmol) in CH2Cl3 (83 mL) was added TFA (83 mL). The reaction was stirred at room temperature for 1 h. The reaction was concentrated and then partitioned between CH2Cl2 and saturated aqueous NaHCO3 solution. The aqueous layer was basified to pH>12 by adding 1N NaOH solution and extracted with Ch2Cl2. The combined organic layers were dried over MgSO4 and concentrated. The crude product was adsorbed onto silica gel and purified by column chromatography (70-100% EtOAc/hexanes. The EtOAc contained 2% NH4OH and was stirred to maintain the mixture) to provide (R)-N-((R)-(2-amino-4-methylthiazol-5-yl)(2-chlorophenyl)methyl)-2-methylpropane-2-sulfinamide and (R)-N-((S)-(2-amino-4-methylthiazol-5-yl)(2-chlorophenyl)methyl)-2-methylpropane-2-sulfinamide and a mixture of both diastereomers (7.1 g, 47%). First eluted product (Isomer A) (white solid, 3.0 g, 20%, >99% de); 1H NMR (400 MHz, CDCl3) δ 7.60 (dd, J=1.6, 7.7 Hz, 1H), 7.38-7.22 (m, 3H), 6.15 (d, J=2.5 Hz, 1H), 4.94 (s, 2H), 3.87 (d, J=2.3 Hz, 1H), 2.34 (s, 3H), 1.27 (s, 9H); HPLC ret. time 3.08 min, 10-99% CH3CN, 15 min run; ESI-MS 358.3 m/z (MH+). Second eluted product (Isomer B) (yellow waxy solid, 5.0 g, 33% 98% de); 1H NMR (400 MHz, CDCl3) δ 7.64 (dd, J=7.7, 1.7 Hz, 1H), 7.36 (dd, J=7.8, 1.4 Hz, 1H), 7.32-7.21 (m, 2H), 6.19 (d, J=1.8 Hz, 1H), 4.86 (s, 2H), 3.65 (d, J=1.2 Hz, 1H), 2.33 (s, 3H), 1.26 (s, 9H); HPLC ret. time 3.77 min, 10-99% CH3CN, 15 min run; ESI-MS 358.3 m/z (MH+).

Provenance & Evidence