L-Threonine, N-(triphenylmethyl)- synthesis

Yield:80514-76-7 59%

Reaction Conditions:

Stage #1: L-threoninewith chloro-trimethyl-silane in dichloromethane; for 0.333333 h;Inert atmosphere;Reflux;
Stage #2: with triethylamine in dichloromethane at 0; for 1.08333 h;Inert atmosphere;
Stage #3: trityl chloridewith triethylamine in methanol;dichloromethane at 20; for 20 h;Inert atmosphere;

Steps:

4.2.1.12. N-Triphenylmethyl-(S)-serine (13).

General procedure: 4.2.1.12. N-Triphenylmethyl-(S)-serine (13). To a suspension of S-serine (2.0 g, 18 mmol) in DCM (26 ml) under a nitrogen atmosphere, was added Me₃SiCl (7.5 ml, 57 mmol) and the solution was stirred at reflux temperature for 20 min. The solution was allowed to cool to 0 °C and Et₃N (8.3 ml, 57 mmol) in DCM (26 ml) was added dropwise over 10 min to the solution, which was then stirred for 45 min. The solution was cooled to 0 °C and anhydrous methanol (0.9 ml) was added dropwise. The solution was allowed to warm to room temperature, and Et₃N (7.0 ml, 18 mmol) was added followed by triphenylmethyl chloride (4.6 g, 18 mmol), and the solution was stirred for 20 h at ambient temperature. An excess of Et₃N (13 ml) and then methanol (94 ml) was added until the white solid present in the mixture was dissolved. The excess solvent was then removed in vacuo producing a white solid. The white solid was partitioned between ethyl acetate (67 ml) and citric acid (40.2 ml, 5% aq w/v), which had been pre-cooled to 4 °C. The organic layer was washed with 2 M aqueous sodium hydroxide (220 ml) followed by water (315 ml). The aqueous layers were combined, washed with ethyl acetate (15 ml) and neutralised with glacial acetic acid (3e4 ml) at 0 °C. The precipitated product was extracted with ethyl acetate (630 ml) and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuoto produce a white solid (3.1 g, 48%).

References:

O'Brien, Keith;ó Proinsias, Keith;Kelleher, Fintan [Tetrahedron,2014,vol. 70,# 34,p. 5082 - 5092]