反応手順
A THF solution (75 mL) of (R)-Cbz-serine (5.30 g, 22.0 mmol) was stirred and cooled at −78° C. under Ar and then 4-methylmorpholine (NMM) (2.9 mL, 26.4 mmol) was added dropwise. After 2 min of stirring at this temperature, isobutylchloroformate (IBCF) (3.5 mL, 26.4 mmol) was added dropwise leading to the precipitation of a white solid, and the reaction was allowed to proceed for additional 2 min. 4-Methoxymethylbenzylamine (4.00 g, 26.4 mmol) was added portionwise at −78° C. and the mixture was stirred at room temperature (2 h). The white solid was filtered and the organic layer was concentrated in vacuo. The residue was triturated with EtOAc resulting in a solid that was filtered and recrystallized with EtOAc to give (R)-2-N-(benzyloxycarbonyl)amino-3-hydroxy-N-(4-methoxymethy (benzyl) propanamide as a white solid (7.20 g, 88%): Rf=0.63 (EtOAc); mp 138-140° C.; [α]25.8D −34.0° (c 1, DMSO); IR (nujol) 3385, 3294, 3106, 2923, 2859, 1690, 1646, 1544, 1458, 1373, 1307, 1243, 1098, 1028, 919, 738, 694 cm−1; 1H NMR (CDCl3) δ 3.36 (s, OCH3), 3.64 (dd, J=5.1, 10.8 Hz CHH′OH), 3.88-4.06 (br d, CHH′OH), 4.19-4.29 (m, CH), 4.34-4.45 (m, CH2OCH3, NCH2), 5.06 (s, CH2O), 6.96 (d, J=7.2 Hz, OC(O)NH), 7.02-7.14 (br s, NH), 7.19 (d, J=7.8 Hz, 2 ArH), 7.27 (d, J=7.8 Hz, 2 ArH), 7.30-7.38 (m, 5 ArH); 13C NMR (CDCl3) δ 43.2 (NCH2), 55.5 (OCH2CH), 58.1 (CH3O), 62.7 (OCH2CH), 67.3 (CH2O), 74.3 (CH2OCH3), 127.6, 128.0, 128.1, 128.3, 128.5, 135.9, 137.0, 137.5 (8 ArC), 156.7 (OC(O)N), 170.7 (C(O)); HRMS (M+H+)(ESI+) 373.1764 [M+H+] (calcd for C20H24N2O5H+ 373.1763); Anal. Calcd. for C20H24N2O5.0.25H2O: C, 63.73; H, 6.55; N, 7.43. Found: C, 63.35; H, 6.43; N, 7.29.
