Hydrochloric Acid → (1S, 2R)-1-phenyl-2-hydroxymethylcyclopropane carboxylic anhydride

Participants

Reaction Steps

8.58 g (0.22 mmol) of sodium amide was suspended in 40 ml of anhydrous benzene. To the resultant suspension was dropwise added a solution of 11.5 ml (0.10 mol) of phenylacetonitrile in 20 ml of anhydrous benzene in a stream of argon gas at 0° C. After completion of the addition, the resultant mixture was stirred at room temperature for 3 hours to effect a reaction. To the resultant reaction mixture was dropwise added a solution of 6.8 ml (0.087 mol) of (R)-(-)-epichlorohydrin in 20 ml of anhydrous benzene while cooling with ice. After completion of the addition, the resultant mixture was stirred at room temperature for 2 hours to effect a reaction. After completion of the reaction, the resultant reaction mixture was subjected to distillation under reduced pressure to thereby remove the solvent and obtain a residue. 20 ml of ethanol and 10 ml of an aqueous 1N-KOH solution were added to the obtained residue, and the resultant mixture was refluxed for 15 hours to effect a reaction. After completion of the reaction, 12N hydrochloric acid was added to the mixture which cooling with ice to thereby acidify the mixture. The acidified mixture was concentrated under reduced pressure to thereby obtain a residue. A saturated aqueous sodium hydrogencarbonate solution was added to the obtained residue, and ethyl acetate was further added for extraction to obtain an organic layer. The organic layer was separated, washed with saturated saline, dried over anhydrous sodium sulfate, and subjected to distillation under reduced pressure to thereby remove the solvent and obtain a residue. The obtained residue was purified by silica gel column chromatography (the composition of the developing solvent was; ethyl acetate:hexane=1:3). As a result, 10.1 g (0.058 mol) of compound 1 (yield: 58%) was obtained as a yellow oily product.

Provenance & Evidence