Sodium hydride → Ethyl 2-(4-methoxybenzyl)-3-oxo-4,4,4-trifluorobutanoate

HRID 247807Notes

Reaction equation

HRID 247807 reaction equation
[H-].[Na+].[H][H].[F:5][C:6]([F:16])([F:15])[C:7](=[O:14])[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10].[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Cl)=[CH:21][CH:20]=1>C(O)C.C(OCC)C>[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][CH:8]([C:7](=[O:14])[C:6]([F:15])([F:16])[F:5])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 67793Ethyl 4,4,4-trifluoroacetoacetateHCID 699934-Methyloxybenzyl chlorideHCID 178418361HCID 178418361, compound

Product 1

HCID 21993363Ethyl 2-(4-methoxybenzyl)-3-oxo-4,4,4-trifluorobutanoate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A 1 L four neck round bottom flask, fitted with reflux condenser, dropping funnel, argon inlet, and magnetic stirrer was charged with 7.17 g (0.149 mol) of a 50% (w/v) oil dispersion of sodium hydride and 300 mL of dry ethyl ether. Absolute ethanol (9.0 mL) was slowly added to the stirred solution. After the evolution of hydrogen stopped, a mixture of 25 g (0.136 mol) of ethyl 4,4,4-trifluoroacetoacetate and 21.3 g (0.136 mol) of 4-methoxybenzyl chloride was added over a 1 hour period. The resulting mixture was refluxed overnight, cooled, extracted with water, 1N hydrochloric acid, dried over anhydrous magnesium sulfate and rotary-evaporated under reduced pressure. The crude reaction mixture (33.5 g) was chromatographed on a 60 mm xx 300 mm silica gel column with ethyl acetate/hexane (25/75). Similar fractions were combined and gave 9.4 g (23%) of the (spectroscopically complex) product as an oil. NMR(CDCl3): 1.26(m,3H), 3.77(s,3H), 4.12(m,2H), 7.08(m,2H).

Workup

  1. temperaturewith reflux condenser
  2. additionwas added over a 1 hour period
  3. temperatureThe resulting mixture was refluxed overnight
  4. temperaturecooled
  5. extractionextracted with water, 1N hydrochloric acid
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customrotary-evaporated under reduced pressure
  8. customThe crude reaction mixture (33.5 g)
  9. customwas chromatographed on a 60 mm xx 300 mm silica gel column with ethyl acetate/hexane (25/75)
  10. customgave 9.4 g (23%) of the (spectroscopically complex) product as an oil

Sources & evidence

ORD record
ord-7725d577424347219d2815dc8fe71d1c
Source dataset
uspto-grants-1993_05
Patent number
US05208143

Reaction notes

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