Triethylamine → alpha-isothiocyanato-(L)-valine methyl ester

Participants

Reaction Conditions

Reaction Steps

A suspension of 1.0 g (5.96 mmol) of (L)-valine methyl ester in 10 ml of chloroform was cooled to -20° C. and treated with a solution of 0.48 ml of thiophosgene in 5 ml of chloroform. The resulting solution was treated dropwise with 2.49 ml (17.9 mmol) of triethylamine, stirred at -20° C. for 15 min, then quenched with 10 ml of 0.1M HCl. The chloroform layer was separated, washed with four 5 ml portions of water, dried over MgSO4, and concentrated in vacuo to provide 1.01 g of the α-isothiocyanato-(L)-valine methyl ester as an oil. The crude oil (1.01 g) was taken up in 10 ml of dichloromethane and added to a mixture of 0.81 g (4.15 mmol) of the resultant compound of Example 3C and 1.14 ml (10.4 mmol) of 4-methylmorpholine in 40 ml of dichloromethane. The resulting mixture was stirred at ambient temperature for 16 h, washed with three 15 ml portions of water, dried over MgSO4, and concentrated in vacuo. Silica gel chromatography of the residue using 15% ethyl acetate in dichloromethane provided 1.23 g (100%) of the desired compound as an oil. 1H NMR (CDCl3) δ1.02 (d, J=7 Hz, 3 H), 1.06 (d, J=7 Hz, 3 H), 2.33 (m, 1 H), 3.40 (s, 3 H), 3.74 (s, 3 H), 4.83 (AA', 2 H), 5.10 (dd, J=8, 5 Hz, 1 H), 7.27 (dd, J=8, 5 Hz, 1 H), 7.33 (d, J=8 Hz, 1 H), 7.73 (br t, J=8 Hz, 1 H), 8.56 (dd, J=5, 1 Hz, 1 H). Mass spectrum: (M+H)+ =296.

Provenance & Evidence