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 δ1.43(s,d,12H); 1.80-2.10(m,2H); 2.23-2.36(m,2H); 3.72(s,3H); 3.76(s,3H); 4.15-4.27(m,1H); 4.50-4.60(m,1H); 5.11(b s,2H); 5.76(b s,1H); 6.38(b s,1H); 6.47(b t,1H); 6.81(b s,1H); 7.34(m,5H); 13C-NMR: 17.82(--CHCH3 ; 24.33(--C H2 --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(MH--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