Iodoethane → N-(tert-Butoxy(hydroxy)methylidene)-O-ethylserine

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Reaction Steps

To a suspension of sodium hydride (17.73 g, 702 mmol) in THF (600 mL) at 0° C. was added MeOH (18 mL) dropwise. The mixture was stirred at RT for 1 h to yield a sodium methanolate solution. Iodoethane (25.5 mL, 316 mmol) and a portion of the sodium methanolate solution (120 mL) were added to a solution of (S)-2-(tert-butoxycarbonylamino)-3-hydroxypropanoic acid (18 g, 88 mmol) in THF (600 mL). After stirring at RT for 1 h, the remaining sodium methanolate solution (480 mL) was added, followed by additional iodoethane (9.9 mL, 123 mmol). The mixture was stirred at RT overnight. The mixture was subsequently concentrated and the residue was dissolved in water. The aqueous layer was washed with ether (250 mL), acidified to pH 2 using 1N HCl, and extracted with EtOAc (3×300 mL). The combined organic layers were washed with 1M Na2S2O3 (300 mL), dried, and concentrated. The resulting crude material was reconstituted in MeOH, DCM and DMF (total volume: 50 mL) and purified via reverse phase preparative HPLC. The fractions were collected and the ACN was removed via rotary evaporation. The resulting aq solution was neutralized with saturated aq NaHCO3, washed with EtOAc (2×200 mL), dried over Na2SO4, filtered, and the organic phase stripped to dryness via rotary evaporation to yield the title compound as a clear oil (1.81 g, 9%). [M+H] calc'd for C10H19NO5, 234. found, 234.

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