[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][O:14][CH:15]([F:17])[F:16])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC(C)C)=O.[F:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH2:39])=[CH:36][CH:35]=1>C1COCC1.C(OCC)(=O)C>[F:16][CH:15]([F:17])[O:14][CH2:13][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:10]([NH:39][CH2:38][C:37]1[CH:40]=[CH:41][C:34]([F:33])=[CH:35][CH:36]=1)=[O:12]
To a solution of (2R)-2-[(tert-butoxycarbonyl)amino]-3-(difluoromethoxy)propanoic acid (780 mg, 3.05 mmol) and triethylamine (924 mg, 9.15 mmol) in THF (15 mL) at −78° C., isobutyl chloroformate (417.7 mg, 3.05 mmol) was added dropwise. After 30 minutes, (4-fluorobenzyl)amine (458 mg, 3.0 mmol) was added and the reaction mixture was allowed to warm up to room temperature. The mixture was then 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 hexanes (1:3) to give tert-butyl {(1R)-1-[(difluoromethoxy)methyl]-2-[(4-fluorobenzyl)amino]-2-oxoethyl}carbamate (870 mg, 78.7%) as a white solid. 1H NMR (300 MHz, CDCl3): δ(ppm) 7.23 (dd, 2H), 7.03 (t, 2H), 6.60 (b, 1H), 6.23 (wt, 1H), 5.24 (w, 1H), 4.3-4.51 (m, 4H), 4.02 (dd, 1H) and 1.45 (s, 9H).
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