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

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Reaction Steps

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:

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