Acetic Acid → HCID 131726781, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of N-carboxybenzyloxy-(2S,3S)-4-fluorothreonine 102 (0.060 g, 0.22 mmol) in DMF (3 ml) was added tert-butyldimethylsilyl chloride (0.073 g, 0.49 mmol) and imidazole (0.033 g, 0.49 mmol). The solution was gently heated at 80° C. for 18 hours. After allowing the solution to cool to room temperature, the solution was diluted with dichloromethane (15 ml) and washed with 1N HCl solution (3×10 ml). The organic layer was dried (MgSO4) and the solvent was removed in vacuo to give a yellow oil. The residue was redissolved in a 1:1 THF/methanol solution (4 ml) and upon stirring 50% aqueous acetic acid (2 ml) was added. After stirring the solution vigorously for 4 hours the solvent was removed in vacuo to give a yellow oil. Trace amounts of acetic acid were removed by treatment of the residue in ethyl acetate (5 ml) with saturated sodium hydrogen carbonate solution (10 ml). The organic layer was dried (MgSO4) and the solvent removed in vacuo to afford N-carboxybenzyloxy-O-tert-butyldimethylsilyl-(2S,3S)-4-fluorothreonine 103 as a pale yellow oil (0.073 g, 86% yield); 1H (400 MHz, CDCl3) 9.50 (1H, bs, OH, exchange with CH3OD), 7.60-7.20 (5H, m, Ph), 6.25, 5.75 and 5.45 (1H, 3×d, J 9.1, NH, exchange with CH3OD), 5.20-5.10 (2H, m, CH2Ph), 4.75-4.20 (4H, H-2, H-3, 4-CH2), 1.00-0.80 (9H, 2×s, SiC(CH3)3), 0.15-0.00 (6H, m, Si(CH3)2); 19F (376 MHz, CDCl3) −224.82 and −225.39 (2×dtJ 47, 4 due to rotamers).

Provenance & Evidence