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

Temperatur

-20 °C

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.

1. customquenched with 10 ml of 0.1M HCl
2. customThe chloroform layer was separated
3. washwashed with four 5 ml portions of water
4. dry with materialdried over MgSO4
5. concentrationconcentrated in vacuo

ORD-Eintrag

ord-7e0e166a4cee41db9ac159ddf905c637

Quelldatensatz

uspto-grants-1994_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05354866