Sodium hydride → HCID 12694071, compound

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Reaction Steps

To 1.404 g of sodium hydride (from 2.87 g of a 50% dispersion), under nitrogen, is added 120 ml of sieve-dried dimethylsulfoxide. The mixture is stirred in an 80°-85° C. bath for 35 minutes, then cooled to room temperature. A solution of 14.0 g of the free base 4-(3-fluorobenzylthio)-4-(2-fluorophenyl)-1-methylpiperidine of Example 55a in 47 ml of DMSO is added over 60 seconds and the solution stirred for one hour. The reaction is then poured into 700 ml of ice water and extracted with three 200 ml portions of dichloromethane. The combined dichloromethane extracts are washed with three 300 ml portions of water and one 75 ml portion of saturated sodium chloride solution, and dried over magnesium sulfate to an oil. The oil is chromatographed on alumina with ether to give crystals. A portion of this, in ether is treated with ethereal maleic acid. The resulting salt is washed with ether and dried to give a powder of 3-(3-fluorophenyl)-1,3-dihydro-1'-methylspiro[benzo(c)thiophene-1,4'-piperidine] maleate, m.p. 137°-140° C. A twice recrystallized portion melts at 138.5°-140.5° C. [Upon continued heating, a new crystalline form develops which collapses in the 175°-180° C. range.

Provenance & Evidence