4-Methylmorpholine → N-[N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanyl]-3-mercapto-D-valine, methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of Nα -Boc-phenylalanine (10.0 in 50 mL of methylene chloride (CH2Cl2) was cooled to -78° C. under an argon atmosphere. To this magnetically-stirred solution was added N-methylmorpholine (NMM) (3.8 g, 37.7 mmol) and isobutylchloroformate (IBCF) (5.15 g, 37.7 mmol). The reaction was allowed to slowly warm to 0° C., and then was maintained at this temperature for 45 minutes. The mixture was then recooled to -78° C., and treated with 3.8 g (37.7 mmol) of NMM and 7.5 g (37.7 mmol) of D-penicillamine methylester hydrochloride. After the reaction had warmed to room temperature and was stirred for 18 hours, it was diluted with 600 mL of ethyl acetate (EtOAc) and washed with 3×175 mL of 0.5 N potassium bisulfate (KHSO4) and 150 mL of a saturated aqueous sodium chloride solution (brine). The organic solution was then dried over anhydrous sodium sulfate (Na2SO 4), filtered, and stripped of all solvent under reduced pressure. The white solid residue title product was obtained in 91% yield (14.07 g).

Provenance & Evidence