4-Methylmorpholine → HCID 12877299, compound

Participants

Reaction Steps

First benzyloxycarbonyl-L-phenylalanyl-D-alanine methyl ester was prepared, as follows. A solution of 0.56 g of D-alanine methyl ester hydrochloride in 6 ml tetrahydrofuran was cooled to 0° C. and then treated with 0.53 ml of N-methylmorpholine. After 15 min of stirring, 1.20 g of benzyloxycarbonyl-L-phenylalanine and 1.08 g of 1-hydroxybenzotriazole were added. A cold solution of 0.99 g of N, N'-dicyclohexylcarbodiimide in 2 ml tetrahydrofuran was then added and the mixture stirred for 1 hour at 0° C., then overnight at room temperature. After adding 0.3 ml of glacial acetic acid, the mixture was stirred 5 min., filtered, and the filtrate concentrated in vacuo to dryness. The residue was dissolved in CHCl3, washed 3 times with 5% aqueous NaHCO3, dried over anhydrous Na2SO4, and the solvent removed in vacuo. The residue was purified by silica gel column chromatography (silica 60 g) using CHCl3 followed by CHCl3 -acetone 10:1 as eluant. Appropriate fractions were pooled and the solvent removed in vacuo to obtain 0.74 g of white solid, m.p. 134-136 C. TLC on silica gel using an eluant of 10 acetone gave Rf =0.37.

Provenance & Evidence