C(O[C:6]([NH:8][C@H:9]([CH2:13][O:14][CH:15]([F:17])[F:16])[C:10]([OH:12])=O)=[O:7])(C)(C)C.[CH2:18](N(CC)CC)C.ClC(OCC(C)C)=O.[CH2:33]([NH2:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C1COCC1.C(OCC)(=O)C>[C:6]([NH:8][C@H:9]([CH2:13][O:14][CH:15]([F:16])[F:17])[C:10]([NH:40][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:12])(=[O:7])[CH3:18]
To a solution of (2R)-2-[(tert-butoxycarbonyl)amino]-3-(difluoromethoxy)propanoic acid (197 mg, 1.0 mmol) and triethylamine (303 mg, 3 mmol) in THF (10 mL) at −78° C., isobutyl chloroformate (174 mg, 1.28 mmol) was added dropwise. After 30 minutes, benzylamine (161 mg, 1.5 mmol) was added and the reaction mixture allowed to warm up to room temperature. The mixture then was diluted with ethyl acetate and washed with water, 0.5N HCl and Brine. The organic layer was dried over magnesium sulphate, concentrated, and triturated with ether-hexanes (1:3) to give (2R)-2-(acetylamino)-N-benzyl-3-(difluoromethoxy)propanamide (48 mg, 16.7%) as a white solid. 1H NMR (300 MHz, CDCl3): δ(ppm) 7.25-7.39 (m, 5H), 6.68 (w, 1H), 6.42 (d, 1H), 6.24 (wt, 1H), 4.73 (m, 1H), 4.48 (d, 2H), 4.24 (dd, 1H), 4.01 (dd, 1H) and 2.05 (s, 3H).
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