Triethyl phosphonoacetate → ethyl (RS)-[3-oxo-2-(2,2,2-trifluoroethyl)-6-trifluoromethyl-2,3-dihydro-1H-isoindol-1-yl]acetate
Reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:16])[CH2:7]P(OCC)(OCC)=O)[CH3:4].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]>CC(=O)OCC>[CH2:3]([O:5][C:6](=[O:16])[CH2:7][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:34])([F:35])[F:36])[CH3:4]Participants
Procedure
0.84 g of NaH were suspended using 60 ml of DME(anhydrous) and 4.5 ml of (diethoxy-phosphoryl)-acetic acid ethyl ester added at a temperature between 10° C. and 25° C. The mixture was stirred at ambient temperature for 30 minutes followed by addition of a solution of 4.2 g of 3-hydroxy-2-(2,2,2-trifluoro-ethyl)-5-trifluoromethyl-2,3-dihydro-isoindol-1-one in 20 ml DME(anhydrous). The reaction mixture was refluxed for 1 h, then cooled to ambient temperature. 100 ml of EA were then added and the mixture washed twice using 200 ml of a semisaturated aqueous NaHCO3-solution. The organic layer was dried over MgSO4 and the solvent was removed in vacuo. Chromatography was performed on Merck Lichrospher RP18, 10 μm, 50*250 mm. Conditions as follows:
Workup
- additionadded at a temperature between 10° C. and 25° C
- temperatureThe reaction mixture was refluxed for 1 h
- temperaturecooled to ambient temperature
- washthe mixture washed twice
- dry with materialThe organic layer was dried over MgSO4
- customthe solvent was removed in vacuo
Sources & evidence
- ORD record
- ord-3d2934efb30d4012af3a08c692437954
- Source dataset
- uspto-grants-2009_09
- Patent number
- US07589117B2
Reaction notes
Loading…