Dicyclohexylcarbodiimide → boc-D-Trp (+/-) trans-2,5-dicarbethoxypyrrolidine

Participants

Reaction Steps

3.9 g (19 mmol) of 1,3-dicyclohexylcarbodiimide (DCC) was added at 0° C. to a solution containing 1.63 g (7.58 mmol) of (±)-trans -2,5dicarbethoxypyrrolidine (1), 2.54 g (11 mmol) of Boc-D-tryptophan, 2.56 g (19 mmol) of 1-hydroxy benzotriazole hydrate, 3.3 ml (19 mmol) of diisopropyloethylamine in 25 ml of dry dimethylformamide (DMF). The resulting clear colorless solution was stirred under an argon atmosphere at room temperature for a period of 18 hr which resulted in the formation of a white precipitate. TLC analysis of the mixture (97:3 CHCl3 /MeOH) indicated that there was some remaining pyrrolidine diester. Therefore, an 2.0 g of DCC was added and the solution was stirred for an additional 5 hr at room temperature. Ethyl acetate (80 ml) was added to the reaction mixture and the solution was washed with water (3×25 ml) and brine solution (1×25 ml), and dried over MgSO4. Solvents were removed in vacuo and to produce 4.53 g of a thick yellow oil. Chromatography of the crude product on silica gel using the eluent showed that the product was a diastereomeric mixture (Rf=0.29 and 0.25) of the coupled products in an approximate ratio of 1.5:1. Total yield for both of the fractions containing the tryptophan pyrrolidine diester was 1.69 g (44.6%). The diastereomer possessing the higher Rf (0.29) was separated and analyzed yielding the following 1H NMR (CDCl3, 360 MHz) spectroscopic data:

Provenance & Evidence