Sodium Sulfate → HCID 86738230, compound

Participants

Reaction Steps

To a suspension of 0.66 g of lithium aluminum hydride in 50 ml of anhydrous tetrahydrofuran is added, dropwise at room temperature under nitrogen, a solution of 2.93 g of cis-1-cyclopropylcarbonyl-4-(4-fluorophenoxy)-3-phenylpiperidine in 50 ml of tetrahydrofuran. After the addition is complete the mixture is refluxed for 30 minutes, cooled, diluted with 50 ml of ether and cautiously treated with saturated sodium sulfate solution at 0°-10° C. until a flocculent white precipitate is obtained. The solid is filtered, washed with ether and the filtrate concentrated in vacuo. The residue is dissolved in ether (150 ml), washed with saturated sodium chloride solution (75 ml), dried overnight over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a colorless gum. The gum is dissolved in ether (80 ml) and treated dropwise with a solution of 1.04 g of fumaric acid in a mixture of ethanol (15 ml) and ether (60 ml). After stirring for a few hours the colorless solid is filtered, washed with ether and dried to afford a salt. A second crop of solid is obtained from the filtrate. The solids are combined and recrystallized from 25 ml of boiling isopropanol to afford a crystalline solid. The solid and mother liquor are combined and the free base is regenerated. The nearly colorless gum is dissolved in 25% methanol/acetone solution and passed through a small silica gel column. The material thus obtained is dissolved in ether (50 ml) and treated dropwise with a solution of 0.91 g of fumaric acid in a mixture of ethanol (15 ml) and ether (60 ml). After stirring the mixture overnight, the solid is filtered, washed with ether and dried to yield product as a colorless solid, mp 167°-168.5° C.

Provenance & Evidence