[F:1][C:2]([F:15])([F:14])[C@@:3]([OH:13])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=O.[F:16][C:17]1[C:22]([CH2:23][NH2:24])=[CH:21][C:20]([CH3:25])=[CH:19][N:18]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C)C=O>[F:14][C:2]([F:1])([F:15])[C@@:3]([OH:13])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([NH:24][CH2:23][C:22]1[C:17]([F:16])=[N:18][CH:19]=[C:20]([CH3:25])[CH:21]=1)=[O:6]A solution of (2R)-3,3,3-trifluoro-2-hydroxy-2-phenylpropanoic acid (6-e with R=CF3 and R′=H, 105 mg, 0.48 mmol), the amine (2-e, 67 mg, 0.48 mmol) and diisopropylethylamine (415 uL, 2.4 mmol) in N,N-dimethylformamide (1 mL) was treated at room temperature with benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBop, 274 mg, 0.53 mmol). After 14 h, the reaction mixture was partitioned between ethyl acetate and 0.5N—NaOH. The aqueous layer was removed and the organic layer was washed with 0.5N—HCl. The aqueous layer was removed by filtering through a plastic frit. The organic layer was evaporated in vacuo to give the desired product (3-1); HRMS (M+H)=343.1059; 1H NMR (500 MHz, CDCl3) δ 7.89 (bs, 1 H), 7.63 (m, 2H), 7.43 (m, 3 H), 7.39 (d, 1 H, J=7.8 Hz), 6.67 (br, 1 H), 4.72 (m, 1 H), 4.48 (d, 2H, J=6.1 Hz), 2.26 (s, 3 H); compound 3-3 [(2R)-3,3,3-trifluoro-N-(2-fluoro-5-trifluoromethylbenzyl)-2-hydroxy-2-phenylpropanamide] was prepared by the same procedure (2-fluoro-5-trifluoromethylbenzylamine was purchased from Alfa Aesar); HRMS (M+H)=396.0825; 1H NMR (500 MHz, DMSO-6d) δ 8.95 (t, 1 H), 7.95 (s, 1 H), 7.65 (m, 3 H), 7.39 (m, 5 H), 4.40 (dq, 2 H).
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