L-Methionine → tert-Butyloxycarbonyl-L-glutaminyl-L-methionine

Participants

Reaction Steps

A solution of Boc-L-Gln (Bachem, 4.92 g, 20 mmole) in THF (45 ml) was cooled to -15°, neutralized with N-methylmorpholine (2.2 ml, 20 mmole) and treated with isobutylchlorocarbonate 2.74 g (20 mmole). After 5 min a solution of L-methionine (4.48 g, 30 mmole) and N-methylmorpholine (3.3 ml. 30 mmole) in H2O (45 ml) was added. (Some warming was necessary to obtain a clear solution of the methionine salt). The mixture was stirred and allowed to warm up to room temperature; gradually a clear solution formed. After 1.5 hr the solution was concentrated in vacuo to remove most of the THF and then acidified with a 20% solution of citric acid in H2O. Saturation with NaCl and extraction with EtOAc (3×50 ml), was necessary to isolate the desired material. The organic layer was washed with H2O and evaporated with a stream of N2. The solid residue was suspended in warm EtOAc (100 ml), stirred for 1 hr, filtered, washed with EtOAc and dried. The product (4.75 g, 63%) melted at 149°-150°; [α]D20 -11.8° (c 2, DMF); RfB, 0.60; RfE, 0.73, Glu, 1.0; Met, 1.0. The proton nmr spectrum, in CD3COOD, showed the expected resonances.

Provenance & Evidence