methyl D-alaninate → (Z)-N-[5,6-Didehydro-N6-[(1,1-dimethylethoxy)-carbonyl]-6-(methoxycarbonyl)-N2-[(phenylmethoxy)-carbonyl]-L-lysyl]-D-alanine Methyl Ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 3.3 g of D-alanine methyl ester and 7.1 g of 46c is heated at 140° C. for 10 min, then another 1.6 g of D-alanine methyl ester is added. Heating is continued at 140° C. for an additional 10 min. After cooling to ambient temperature the crude product is chromatographed on silica gel using variable gradient hexane/ethyl acetate. Purified product (6.7 g) is recovered. The material is crystallized from hexanes-ether to give 5.8 g of the desired product 47c as a solid. NMR δ 1.43 (s, d, 12 H), 1.80-2.10 (m, 2 H); 2.33-2.36 (m, 2 H); 3.72 (s, 3 H); 3.76 (s, 3 H); 4.15-4.27 (m, 1 H); 4.50-4.60 (m, 1 H); 5.11 (b s, 2 H); 5.76 (b s, 1 H); 6.38 (b s, 1 H); 6.47 (b t, 1 H); 6.81 (b s, 1 H); 7.34 (m, 5 H); 13C-NMR: 17.82 (--CHcH3 ; 24.33 (--CH2 --CH2); 28.02 (C(CH3)3); 30.99 (--CH2CH=C); 47.94 (--CHCH3); 52.17 (--OCH3); 52.29 (--OCH3); 54.28 (OCCHNH); 66.93 (--CH2Ar); 80.43 (--OC(CH3)3); 126.57 (--HNC=C); 127.86 (phenyl ring carbon); 127.94 (phenyl ring carbon); 128.12 (phenyl ring carbon); 128.28 (phenyl ring carbon); 135.98 (phenyl ring carbon); 153.45 (OCONH); 156.21 (OCONH--); 165.13 (--CONH--); 171.04 (--CO2 --); 172.99 (--CO2 --). IR (KBr, cm-1) 3300(s), 1720(s), 1690(s); 1650(s); 1510(s); MS (CI) m/z 522 (MH)+ ; 466 (MH-C4H8)+ ; 422 (M-C4H8CO2)+. MS (FAB) m/z 544 (M+Na)+ ; 522 (MH)+ ; 466 (MH-C4H8)+ ; Anal Calcd: C, 57.57; H, 6.76; N, 8.06; Found: C, 56.98; H, 6.66; N, 7.88. [α]D26 -7±1; m.p. 120°-121° C.

Provenance & Evidence