[H-].[Na+].[F:3][C:4]([F:11])([F:10])[C:5](OCC)=[O:6].[CH2:12]([O:14][CH:15]([O:20][CH2:21][CH3:22])[CH2:16][CH2:17][C:18]#[N:19])[CH3:13].O>O1CCCC1>[CH2:21]([O:20][CH:15]([O:14][CH2:12][CH3:13])[CH2:16][CH:17]([C:5](=[O:6])[C:4]([F:11])([F:10])[F:3])[C:18]#[N:19])[CH3:22]To a 40°-45° C. stirring suspension of hexanewashed sodium hydride (5.5 g of a 60% dispersion, 0.14 mol) in 200 mL of dried tetrahydrofuran is added dropwise a solution of ethyl trifluoroacetate (15 g, 0.11 mol) and 3-cyanopropionaldehyde diethyl acetal (17 g, 0.11 mol) in 100 mL of dry tetrahydrofuran. The previously gray suspension slowly turns light brown in color. The reaction mixture is stirred at 50°-55° C. overnight before being quenched by slow addition of 2-propanol (15 mL). Rotary evaporation of the volatiles yields a dark oil, to which is added 150 mL of pH 7 water. Unreacted starting materials are conveniently removed by washing the aqueous layer with diethyl ether (3×30 mL). The basic aqueous phase is then acidified with 12 N hydrochloric acid and extracted with ethyl acetate (2×100 mL). The combined organic layers are washed once with saturated sodium bicarbonate (40 mL) and once with brine (15 mL) before being dried over magnesium sulfate. Rotary evaporation yields a reddish oil which is flash chromatographed over silica gel using 4:1 hexane-ethyl acetate as eluent to provide the desired product (9 g, 32%) as a yellow oil.
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