Sodium hydride → HCID 90087791, compound

HRID 1486438Notes

Reaction equation

HRID 1486438 reaction equation
COP([CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])(OC)=O.[H-].[Na+].[F:17][C:18]([F:24])([F:23])[CH:19]([CH3:22])[CH:20]=O>C1COCC1>[F:17][C:18]([F:24])([F:23])[CH:19]([CH3:22])/[CH:20]=[CH:7]/[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27821883,3,3-trifluoro-2-methylpropanalHCID 4564495tert-Butyl Dimethylphosphonoacetate

Product 1

HCID 90087791HCID 90087791, compoundYield 40.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl 2-(dimethoxyphosphoryl)acetate (9.78 g, 43.6 mmol) in THF (10 mL) was slowly transferred to a suspension of NaH (60% dispersion in mineral oil) (1.903 g, 47.6 mmol) in THF (30 mL) at 0° C. under a nitrogen atmosphere. After the addition was complete, the reaction mixture was stirred at 0° C. for 10 min, and then warmed to room temperature. After being stirred for 30 min, the reaction mixture was cooled to 0° C. again, and a solution of 3,3,3-trifluoro-2-methylpropanal (5 g, 39.7 mmol) in THF (10 mL) was added, and the ice bath was removed. After 12 h at 25° C., the mixture was partitioned between water (60 mL) and EtOAc (60 mL). The aqueous layer was extracted with EtOAc (60 mL), and the combined organic layers were successively washed with water (60 mL) and brine. The resulting solution was dried over MgSO4, concentration under reduced pressure, and purified by silica gel flash chromatography (330 g column, 0% to 15% EtOAc in hexane over 20 min) to obtain Intermediate S-5A (3.61 g, 16.10 mmol, 40.6% yield). 1H NMR (400 MHz, chloroform-d) δ 6.77 (dd, J=15.8, 7.7 Hz, 1H), 5.95 (dd, J=15.7, 0.6 Hz, 1H), 3.12-2.93 (m, 1H), 1.56-1.47 (m, 9H), 1.37-1.27 (m, 3H).

Workup

  1. additionAfter the addition
  2. temperaturewarmed to room temperature
  3. stirringAfter being stirred for 30 min
  4. temperaturethe reaction mixture was cooled to 0° C. again
  5. customthe ice bath was removed
  6. waitAfter 12 h at 25° C.
  7. customthe mixture was partitioned between water (60 mL) and EtOAc (60 mL)
  8. extractionThe aqueous layer was extracted with EtOAc (60 mL)
  9. washthe combined organic layers were successively washed with water (60 mL) and brine
  10. dry with materialThe resulting solution was dried over MgSO4, concentration under reduced pressure
  11. custompurified by silica gel flash chromatography (330 g column, 0% to 15% EtOAc in hexane over 20 min)
  12. customto obtain Intermediate S-5A (3.61 g, 16.10 mmol, 40.6% yield)

Sources & evidence

ORD record
ord-8f37d829e76a42a58dce25741aabce62
Source dataset
uspto-grants-2016_08
Patent number
US09427442B2

Reaction notes

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