Dimethylformamide → (2R,3S)-3-(Benzyloxy)-2-[Boc-(methyl)amino]butanoic Acid

Participants

Reaction Steps

In a round bottom flask, under argon atmosphere, commercially available (2R,3S)-3-benzyloxy-2-(tert-butoxycarbonyl-amino)-butanoic acid was dissolved in dry THF (15 mL). Subsequently at 0° C., NaH (60% dispersion in mineral oil, 0.21 g, 5.33 mmol) was added in one portion. The reaction mixture was left to stir at the same temperature for 10 min and then MeI (0.95 mL, 15.22 mmol) followed by DMF (0.75 mL) were sequentially added. The reaction was left for 2.0 h at 0° C. and for 15 h at rt, then quenched with H2O (15 mL), diluted with EtOAc (30 mL) and acidified to pH 2 by dropwise addition of 2.0 N HCl aqueous solution. The organic layer was separated and the aqueous phase was back-extracted with EtOAc (2×30 mL). The organic phase was dried over Na2SO4, filtered and concentrated to dryness. The crude mixture was purified by column chromatography using a Teledyne ISCO apparatus eluting with Cy:TBME (60:40) to give the title compound (1.1 g, 67%), as a mixture of two rotamers (2:1 ratio), as a colorless oil. 1H NMR (DMSO-d6) δ 1.13-1.20 (m, 6H), 1.36 (s, 9H, minor rotamer), 1.41 (s, 9H, major rotamer), 2.84 (s, 3H, minor rotamer), 2.87 (s, 3H, major rotamer), 4.13-4.24 (m, 2H), 4.34-4.40 (m, 2H), 4.49 (d, J=5.5 Hz, 1H, minor rotamer), 4.57-4.62 (m, 2H), 4.71 (d, J=5.2 Hz, 1H, major rotamer), 7.23-7.35 (m, 10H).

Provenance & Evidence