Acetic Acid → N-(t-Butoxycarbonyl)-alpha-(4-hydroxy-2,3,5,6-tetrahydro-4-pyranyl)glycine, benzyl ester

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Reaction Conditions

Reaction Steps

A solution of diisopropylamine (17.5 ml, 0.127 moles) in 300 ml of dry tetrahydrofuran at -45° C. under argon was treated with 70 ml (0.117 moles) of 1.71M n-butyllithium (in hexane). After 20 minutes at -45° C., the mixture was cooled to -72° C. and treated with 13.3 g (0.05 moles) of dried N-(t-butoxycarbonyl)glycine, benzyl ester in 60 ml of dry tetrahydrofuran. After 50 minutes, the dark yellow homogeneous solution was treated with 5 ml (5.43 g, 0.0543 moles) of tetrahydro-4-pyranone in 50 ml of tetrahydrofuran and the temperature allowed to rise to 0° C. over 1.5 hours. A solution of 7.2 g (0.12 moles) of glacial acetic acid in 20 ml of tetrahydrofuran was added to the purple solution, and the resulting light yellow turbid mixture was poured into 1L of water and extracted with ethyl acetate. The organic layer was washed with 2% potassium bisulfate, 5% sodium bicarbonate and brine, dried (sodium sulfate) and evaporated to an oil. Chromatography on 800 ml of LPS-1 in hexane:ethyl acetate (1:1) and combination of the product fractions (Rf=0.32 in the same solvent) gave an oil which solidified on trituration with hexane yielding a total of 10.34 g of product as a white solid, melting point 90°-93° C.

Provenance & Evidence