Dimethylformamide → N-[(1,3-Dimethlindole-2-carbonyl)valinyl]-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester

Participants

Reaction Conditions

Reaction Steps

4-Dimethylaminopyridine (DMAP) (67 mg, 0.55 mmol) and 1-(3′-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC) (125 mg, 0.65 mmol) were added as solids to a DMF solution of 1,3-dimethylindole-2-carboxylic acid (95 mg, 0.5 mmol in 1 mL of DMF), and the resultant reaction mixture was stirred for 10 minutes under a nitrogen atmosphere at 0° C. A methylene chloride solution of N-(valinyl)-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester (153 mg, 0.5 mmol in 1 mL of methylene chloride) was added and the resultant reaction mixture was first stirred for 1 hour at 0° C. and then for 4 hours at room temperature. The reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution and the aqueous solution was back-extracted with ethyl acetate. The combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×), and brine, dried over sodium sulfate, and concentrated to give a solid. The solid was triturated with ether/hexane to yield the title product as a white solid (134 mg, 56%). TLC (ethyl acetate/hexanes, 2:1): Rf=0.42. 1H-NMR (CDCl3): δ 7.59 (d, J=8.8, 1 H), 7.37 (d, J=7.7, 1 H), 7.29-7.24 (m, 1 H), 7.12-7.07 (m, 1 H), 4.49-4.26 (m, 5 H), 3.81-3.79 (m, 3 H), 2.66-2.47 (m, 5 H), 2.22-2.10 (m, 1 H), 1.45-1.41 (m, 9 H, 1.09-1.03 (m, 6 H).

Provenance & Evidence