Water → 3-Trifluoroacetyl-3-cyanopropionaldehyde diethyl acetal

HRID 1940991Notes

Reaction equation

HRID 1940991 reaction equation
CCCCCC.[F:7][C:8]([F:15])([F:14])[C:9](OCC)=[O:10].[CH2:16]([O:18][CH:19]([O:24][CH2:25][CH3:26])[CH2:20][CH2:21][C:22]#[N:23])[CH3:17].O>O1CCCC1>[CH2:25]([O:24][CH:19]([O:18][CH2:16][CH3:17])[CH2:20][CH:21]([C:9](=[O:10])[C:8]([F:15])([F:14])[F:7])[C:22]#[N:23])[CH3:26]

Participants

6

Reactant 4

HCID 962WaterHCID 8058HexaneHCID 9794Ethyl trifluoroacetateHCID 876164,4-Diethoxybutanenitrile

Product 1

HCID 214595343-Trifluoroacetyl-3-cyanopropionaldehyde diethyl acetalYield 32.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 40°-45° C. stirring suspension of hexane-washed 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 12N 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.

Workup

  1. washwashed sodium hydride (5.5 g of a 60% dispersion, 0.14 mol) in 200 mL of dried tetrahydrofuran
  2. stirringThe reaction mixture is stirred at 50°-55° C. overnight
  3. custombefore being quenched by slow addition of 2-propanol (15 mL)
  4. customRotary evaporation of the volatiles
  5. customyields a dark oil
  6. customare conveniently removed
  7. washby washing the aqueous layer with diethyl ether (3×30 mL)
  8. extractionextracted with ethyl acetate (2×100 mL)
  9. washThe combined organic layers are washed once with saturated sodium bicarbonate (40 mL) and once with brine (15 mL)
  10. dry with materialbefore being dried over magnesium sulfate
  11. customRotary evaporation
  12. customyields a reddish oil which
  13. customchromatographed over silica gel using 4:1 hexane-ethyl acetate as eluent

Sources & evidence

ORD record
ord-832c876df50c419181ef78bb19669580
Source dataset
uspto-grants-1997_12
Patent number
US05702681

Reaction notes

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