Water → 3-Trifluoroacetyl-3-cyanopropionaldehyde diethyl acetal

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.

1. stirringThe reaction mixture is stirred at 50°-55° C. overnight
2. custombefore being quenched by slow addition of 2-propanol (15 mL)
3. customRotary evaporation of the volatiles
4. customyields a dark oil
5. customare conveniently removed
6. washby washing the aqueous layer with diethyl ether (3×30 mL)
7. extractionextracted with ethyl acetate (2×100 mL)
8. washThe combined organic layers are washed once with saturated sodium bicarbonate (40 mL) and once with brine (15 mL)
9. dry with materialbefore being dried over magnesium sulfate
10. customRotary evaporation
11. customyields a reddish oil which
12. customchromatographed over silica gel using 4:1 hexane-ethyl acetate as eluent

ORD record

ord-62147e1a486b49fbaf41c870d41f6239

Source dataset

uspto-grants-1994_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05371239