Bromine → HCID 15454950, compound

Participants

Reaction Steps

To a stirred and ice-cooled mixture of crude (2S*,3S*,4R*,5R*)-1-benzyloxycarbonyl-3-[N-(t-butoxycarbonyl)amino]-4-formyl-5-methyl-2-phenylpyrrolidine (3.66 g, 5.90 mmol) and NaHCO3 (19.8 g, 0.24mol) in MeOH--H2O (9:1 by volume; 30 ml) was added a 2.0 M solution of Br2 in MeOH--H2O (9:1; 30 ml, 60 mmol) dropwise. The reaction mixture was stirred at room temperature for 2 hours, during which the color changed from deep red to orange. Sat. Na2S2O3 (hypo) aq. solution was added dropwise to the mixture with ice-cooling, until the orange color due to the excess Br2 was discharged. The mixture was filtered through a pad of Celite, and the filter cake was washed with CH2Cl2. The combined filtrate and washings were concentrated in vacuo. The syrupy residue was diluted with AcOEt--PhMe (2:1, 120 ml), washed with sat. Na2S2O3 aq. solution (×2), sat. NaHCO3 aq. solution (×1), and sat. NaCl aq. solution, dried (MgSO4), and concentrated in vacuo to give a white solid (2.96 g). This was recrystallized from AcOEt-n-hexane to give title compound (2.44 g, 88% in 2 steps from (2S*,3S*,4R*,5R*)-1-benzyloxycarbonyl-3-[N-(t-butoxycarbonyl)amino]-4-hydroxymethyl-5-methyl-2-phenylpyrrolidine) as white powders. mp 147-148 C.; IRmax (nujol): 3310(s), 1728(s), 1701(s, shoulder), 1690(vs), 1537(s), 1535(s), 1280(m), 1165(m), 750(m), 700(s) cm-1 ; 1H-NMR δ: 7.52-7.15(m, 9H), 7.05(br.s, 1H), 5.28(br.d, J=8.1 Hz, 1H), 5.05(br.s, 2H), 4.60(ddd, J=11.7, 8.8, 8.1 Hz, 1H), 4.35-4.17(m, 1H), 4.02(br.d, J=8.8 Hz, 1H), 3.71(s, 3H), 2.58(dd, J=11.7, 9.9 Hz, 1H), 1.62(br.d, J=5.5 Hz, 3H), 1.39(s, 9H) ppm.

Provenance & Evidence