4-Bromoaniline → 1-Methylethyl{(3S)-3-[(4-bromophenyl)amino]butanoyl}carbamate

Participants

Reaction Steps

1-Methylethyl (2E)-2-butenoylcarbamate (for a preparation see Intermediate 11) (9.38 g, 54.8 mmol) was stirred in toluene (281 mL) under nitrogen and (R-BINAP)ditriflatebis(acetonitrile)palladium(II) (Intermediate 24, 3.35 g, 3.01 mmol) added. The catalyst formed a gummy ball, the solution turned to an opaque yellow mixture and was stirred for 20 min. 4-Bromoaniline (14.14 g, 82 mmol) was added, the solution turned to a clear light brown and the gummy catalyst dissolved further. The mixture was stirred for 16 h. Similarly a second batch of 1-methylethyl (2E)-2-butenoylcarbamate (Intermediate 11, 8.51 g, 49.7 mmol) was stirred in toluene (255 mL) under nitrogen and (R-BINAP)ditriflatebis(acetonitrile)palladium(II) (3.04 g, 2.73 mmol) added. The catalyst formed a gummy ball, the solution turned to an opaque yellow mixture and was stirred for 20 min. 4-Bromoaniline (12.83 g, 74.6 mmol) was added, the solution turned to a clear light brown and the gummy catalyst dissolved further. The mixture was stirred for 16 h. The two reaction mixtures were combined and loaded on to a 1.5 kg Isco silica Redisep column. The column was eluted with DCM/MeOH (0%->0.5%, 19 CV). The clean, product containing fractions were evaporated to a pale brown oil. The mixture was dried in a vacuum oven overnight at 40° C. to give a white solid (24.2 g, 67% overall). LCMS (Method C): Rt=0.91, MH+=343. ee=92%.

Provenance & Evidence