Hydrochloric Acid → HCID 20343117, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 8.13 g of 1-benzyl-3-piperidone hydrochloride in a mixture of 28.8 ml of tetrahydrofuran-water (1:1) and 2.99 ml (36 mmoles) of concentrated hydrochloric acid is added 4.687 g (72 mmoles) of potassium cyanide while keeping at a temperature below 8° C., and the mixture is stirred for 4 hours, additionally mixed with 1.495 ml (18 mmoles) of concentrated hydrochloric acid and 1.172 g (18 mmoles) of potassium cyanide, stirred for 1 hour and extracted with ether. The extract is washed with water, dried over magnesium sulfate, and evaporated under reduced pressure. The oily residue is dissolved in 14.4 ml of concentrated hydrochloric acid, heated at 80° C. for 1 hour, cooled and then filtered. The residue is washed with acetone. The combined filtrate and washing are evaporated under reduced pressure to yield syrupy residue, and the latter is adjusted to pH 8 with 0.25 N aqueous sodium hydroxide solution, washed thrice with chloroform, and slowly adsorbed on a column of 200 ml of Amberlite IR 120B (H+). The column is washed with 1 L of water, and the eluate with 1.28 L of 5 N aqueous sodium hydroxide solution is evaporated under reduced pressure. The residue is crystallized from acetone to yield 1-benzyl-3-hydroxypiperidine-3-carboxylic acid 1.3 hydrate (mp. 103.5°-104.5° C.) as prisms in 60.2% yield, and the latter is recrystallized from dimethylformamide-water-acetone to yield the pure crystalline product (mp. 104°-105° C.), and the latter is dried over phosphorus pentachloride at 70° C. for 48 hours to yield the corresponding anhydrous material (mp. 212°-214° C.).

Provenance & Evidence