Chloroacetyl chloride → 4-Chloro-2-cyano-3-hydroxy-but-2-enoic acid tert-butyl ester

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A solution of t-butyl cyanoacetate Compound 1a (32.2 g, 228 mmol, 1.14 M) in THF was added dropwise to a suspension of 60% NaH (9.13 g, 228 mmol) in THF (200 mL) under nitrogen at 0° C. The mixture was stirred until hydrogen gas evolution ceased and the solution became homogeneous. A solution of chloroacetyl chloride Compound 1b (18.5 mL, 228 mmol) in THF (100 mL) was added at a rate sufficiently slow enough to maintain the temperature below 10° C. After stirring for 4 hr, the reaction was quenched at 0° C. with water (25 mL). The resulting precipitate was filtered through Celite 545. The organic solution was then evaporated down to give a residue that was partitioned between ether and 1 M NaOH. The aqueous layer was washed with ether (3×) and adjusted to pH 5 with NaH2PO4. The aqueous layer was extracted with EtOAc, then dried over MgSO4 and evaporated to yield 4-chloro-2-cyano-3-hydroxy-but-2-enoic acid tert-butyl ester Compound 1c (26.3 g) as a light brown foam. 1H NMR (CDCl3) δ 4.34 (br s, 2H), 1.47 (s, 9H). MS 216 (M−).

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