Ethyl Acetate → Prasugrel

Participants

Reaction Steps

2.6 g (7.8 mmole) of 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine pyridine (prepared as described in Example 20) were dissolved in a mixture of 10 ml of dimethylformamide and 5 ml of acetic anhydride, and then 0.35 g (8.6 mmole) of a 60% w/w dispersion of sodium hydride in mineral oil was added to the resulting solution, whilst ice-cooling; the mixture was then stirred for 20 minutes at the same temperature, after which it was stirred for a further 3 hours at room temperature. At the end of this time, 300 ml of ethyl acetate were added to the mixture, which was then washed four times, each time with 50 ml of a saturated aqueous solution of sodium chloride The organic layer was separated and dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was subjected to silica gel column chromatography, using a 100:3 by volume mixture of toluene and ethyl acetate as the eluent, to give a yellow oil. This oil was crystallized from diisopropyl ether, to obtain the title compound as white crystals, melting at 120°-121.5° C., in a yield of 65%.

Provenance & Evidence