Dimethylformamide → Benzyl N-(tert-butoxycarbonyl)-D-alanyl-L-prolinate

Participants

Reaction Steps

A mixture of 10.0 g (0.0529 m) of N-tert.-butoxy-carbonyl-D-alanine, 12.75 g (0.0529 m) of L-proline, benzyl ester hydrochloride, 14.28 g (0.0106 m) of 1-hydroxybenzotriazole, 15 ml of N-methylmorpholine and 125 ml of dry tetrahydrofuran together with 10.9 g (0.0529 m) of dicyclohexylcarbodiimide and 15 ml of dry dimethylformamide, reacted and worked up as described above, gave 20.4 g of crude N-tert.-butoxycarbonyl-D-alanyl-L-proline benzyl ester. Removal of the t-boc protective group, as described, gave D-alanyl-L-proline, benzyl ester hydrochloride, m.p. 140°-142°. This material (8.3 g, 0.0265 m) was condensed with 5.92 g (0.0265 m) of N-carbomethoxymethyl-L-prolinehydrochloride as described, to give 3.1 g of syrupy N-carbomethoxyethyl-L-prolyl-D-alanyl-L-proline, benzyl ester. Barium hydroxide treatment of 3.0 g (6.7 mm) of the above diester gave 2.1 g of N-carboxymethyl-L-prolyl-D-alanyl-L-proline; m.p. 145°-148° [α]D25 =-39.9° (C,1, 1:1 CH3OH.H2O).

Provenance & Evidence