4-Methylmorpholine → Methyl 3-methyl-2-(5-(4-nitrophenyl)thiazole-2-carboxamido)butanoate

Participants

Reaction Steps

N-methyl morpholine (1.01 ml) was added to a solution of 5-(4-nitrophenyl)thiazole-2-carboxylic acid (Intermediate 2, step B, 2.3 g) in THF (72 ml). The reaction mixture was stirred for 10 minutes at RT, cooled to −20° C. Isobutyl chloroformate (1.19 ml) was added and the mixture was stirred for 15-20 minutes at −20 to −30° C. This was followed by the addition of L-valine methyl ester hydrochloride (2.15 g) previously neutralized with Et3N (1.8 ml). The reaction mixture was stirred at −20 to −30° C. for 5 minutes and was then allowed to gradually warm to RT. The solvent was removed under reduced pressure and the crude material was chromatographed on silica gel in 15:85 EtOAc:CHCl3 to get pale yellow colored solid which was crystallized in EtOAc/Pet ether to yield 2.25 g (67%) of the title compound. 1H NMR (DMSO-d6, 300 MHz): δ 8.95 (d, 1H), 8.7 (s, 1H), 8.34 (d, 2H), 8.09 (d, 2H), 4.33 (m, 1H), 3.68 (s, 3H), 2.27 (m, 1H), 0.95 (t, 6H); MS (ES+): m/z 364 (M+1).

Provenance & Evidence