Diisopropylethylamine → Boc-L-phenylalanine methyl ester

Participants

Reaction Steps

To a solution of 4-amino-N-[(1,1-dimethylethoxyl)carbonyl]-L-phenylalanine methyl ester (1.4 g, 4.8 mmol) in DMF (12 mL) were added 2,4-dimethyl-3-pyridinecarboxylic acid hydrocloride (919 mg, 4.9 mmol), HBTU (1900 mg, 5 mmol) and diisopropylethylamine (2.7 mL, 15 mmol) at room temperature. The mixture was stirred for 15 hr and was diluted with 10 mL of ethyl acetate and 10 mL of water. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined extracts were washed with brine and dried over anhydrous magnesium sulfate. Filtration and concentration of the solvent gave a crude product which was purified on silica gel eluting with ethyl acetate:hexane (2:1 to 4:1) to give of 4-[(2,4-dimethyl-3-pyridyl)carbonyl)amino]-N-[(1,1-dimethylethoxyl)carbonyl]-L-phenylalanine methyl ester (226 mg). This compound (220 mg) was treated with 6 mL of 4 N hydrochloric acid in dioxane at room temperature. After 5 minutes, the solid went into solution and the mixture was stirred for 18 hr and was concentrated to give white solid (210 mg). This intermediate was used in the next step synthesis without further purification.

Provenance & Evidence