Glutamic acid diethyl ester hydrochloride → 2-[(5-Bromo-3-methyl-thiophene-2-carbonyl)-amino]-glutamic acid diethyl ester

Participants

Reaction Steps

To a stirred solution of 10.86 g (49.1 mmol) of 5-Bromo-3-methyl-thiophene-2-carboxylic acid (prepared according to D. Spinelli, JCS Perkin Trans. II, 1972, 1866), 6.97 g (51.6 mmol) of 1-Hydroxybenzotriazole hydrate, 9.0 mL (51.7 mmol) of diisopropylethylamine and 12.36 g (51.6 mmol) of L-glutamic acid diethyl ester hydrochloride in 70 mL of DMF was added 9.89 g (51.6 mmol) of 1-(3-Dimethylamino-propy)-3-ethyl-carbodiimide hydrochloride. The reaction mixture was stirred under Argon for 18 hours, poured into H2O and extracted with ethyl acetate. The organic layer was washed sequentially with 0.5 N HCl, saturated NaHCO3 soln and saturated NaCl soln, dried over MgSO4, then concentrated under reduced pressure. This residue was purified by flash chromatography on silica gel eluting methylene chloride-ethyl acetate (20:1). In this manner, there was obtained 19.70 g (99%) of the desired product as a colorless oil.

Provenance & Evidence