Ethyl formate → Ethyl 2-[(2H-1,3-benzodioxol-5-yl)methyl]-3-oxopropanoate

Participants

Reaction Conditions

Reaction Steps

First 2.0 g of 606 NaH was suspended in 30 ml of THF and the suspension solution was cooled to 0° C. Then, 6.0 g of ethyl 3-(3,4-methylenedioxyphenyl)-propionate (purity: 92.1% by weight) was dissolved in 20 ml of THF and added dropwise to the suspension solution prepared above. After 4 ml of ethyl formate was added at 0° C., the solution was returned to room temperature and stirred for a further 20 minutes. The reaction solution was heated to 40° C. and stirring was further continued. About 30 minutes after heating, gas generation was observed. After completion of gas generation, the reaction solution was analyzed by HPLC (Column: LiChrosphere 100 PR-8(E), 250 mm×4.0 mm I.D., manufactured by Merck Ltd., Mobile phase: an aqueous solution of phosphate/potassium dihydrogenphosphate: acetonitrile=1:1, flow rate: 1 ml/minute, detection wavelength: 210 nm, column temperature: 30° C.), it was observed that raw materials remained. Then, 1 g of NaH and 4 ml of ethyl formate were added to the reaction solution and stirred at 40° C. Gas generation started again and completed in about 15 minutes. As the reaction solution was analyzed again, the raw materials were observed to still remain. Then, 1 g of NaH and 4 ml of ethyl formate were added to the reaction solution. After completion of gas generation, the reaction solution was analyzed again. Since the raw materials were observed to slightly remain, further 1 g of NaH and 8 ml of ethyl formate were added to the reaction solution. Since the raw materials were observed to completely disappear, the reaction was terminated. After pH was adjusted to 7 to 8 with hydrochloric acid, ethyl acetate was added to perform extraction. Mineral oil contained in NaH was removed by a separatory funnel in accordance with a liquid-separatory operation. The obtained ethyl acetate layer was concentrated to obtain 4.75 g of the titled compound as an orange oil. The chemical purity, as analyzed in accordance with the process of Example 1, was 80.20% by weight.

Provenance & Evidence