Triethyl phosphonoacetate → ethyl (RS)-[3-oxo-2-(2,2,2-trifluoroethyl)-6-trifluoromethyl-2,3-dihydro-1H-isoindol-1-yl]acetate

HRID 2061633Notes

Reaction equation

HRID 2061633 reaction equation
C(OP([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])(OCC)=O)C.[H-].[Na+].O[CH:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:27]([F:30])([F:29])[F:28])[CH:25]=2)[C:20](=[O:31])[N:19]1[CH2:32][C:33]([F:36])([F:35])[F:34].C(=O)([O-])O.[Na+]>C(COC)OC>[O:31]=[C:20]1[C:21]2[C:26](=[CH:25][C:24]([C:27]([F:28])([F:29])[F:30])=[CH:23][CH:22]=2)[CH:18]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[N:19]1[CH2:32][C:33]([F:35])([F:34])[F:36]

Participants

6

Reactant 4

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 17966419HCID 17966419, compound

Product 1

HCID 57678949ethyl (RS)-[3-oxo-2-(2,2,2-trifluoroethyl)-6-trifluoromethyl-2,3-dihydro-1H-isoindol-1-yl]acetateYield 609.3%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

Under argon, ethyl (diethoxyphosphoryl)acetate (135 mg, 0.6 mmol) was dissolved in anhydrous dimethoxyethane (10 ml). 17.6 mg of NaH (60% in oil) were added at RT to this solution which was stirred at RT for 10 min. Afterward, a solution of 120 mg (0.04 mmol) of (RS)-3-hydroxy-2-(2,2,2-trifluoroethyl)-5-trifluoromethyl-2,3-dihydroisoindol-1-one in anhydrous dimethoxyethane (5 ml) was added and the mixture was subsequently stirred at reflux for 2 h. The reaction solution was left to cool; the reaction solution was then poured onto 50 ml of 5% sodium hydrogencarbonate solution and extracted twice with 20 ml each time of ethyl acetate; the organic phase was dried over MgSO4 and concentrated under reduced pressure, and the residue was purified by chromatography on silica gel using DIP as the eluent. 90 mg (61%) of ethyl (RS)-[3-oxo-2-(2,2,2-trifluoroethyl)-6-trifluoromethyl-2,3-dihydro-1H-isoindol-1-yl]acetate were obtained as a colorless oil which crystallized from heptane as a beige solid.

Workup

  1. stirringthe mixture was subsequently stirred
  2. temperatureat reflux for 2 h
  3. waitThe reaction solution was left
  4. temperatureto cool
  5. extractionextracted twice with 20 ml each time of ethyl acetate
  6. dry with materialthe organic phase was dried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customthe residue was purified by chromatography on silica gel using DIP as the eluent

Sources & evidence

ORD record
ord-31a2bcd96093423781317262670801f4
Source dataset
uspto-grants-2012_10
Patent number
US08283374B2

Reaction notes

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