Sodium Hydroxide → (1r,5s)-6,6-Dimethyl-3-oxabicyclo[3.1.0]hexan-2-one

Participants

Reaction Conditions

Reaction Steps

To 13.5 kg of a solution containing 8.53 kg of ethyl 3-acetoxymethyl-2,2-dimethylcyclopropanecarboxylate obtained in Production Example (39.8 mol, cis body/trans body ratio was 83.4/16.6, (1R)-cis body had an optical purity of 93.4% ee), 9.1 kg of water was added and the temperature thereof was raised up to 50° C., then, 24.2 kg of a 28% sodium hydroxide aqueous solution was dropped over a period of 4 hours, and the mixture was thermally kept at the same temperature for 2 hours. It was confirmed that ethyl 3-acetoxymethyl-2,2-dimethylcyclopropanecarboxylate disappeared and was converted into 3-hydroxymethyl-2,2-dimethylcyclopropanecarboxylic acid, then, to this solution was added 25.6 kg of toluene and the solution was mixed and separated, and the organic layer was removed. Further, to the aqueous layer was added 17.1 kg of toluene and the solution was mixed and separated, and the organic layer was removed likewise. To the resultant aqueous layer was added 21.8 kg of 35% hydrochloric acid at 20° C. and the mixture was thermally kept for 3 hours. It was confirmed that cis-3-hydroxymethyl-2,2-dimethyl-cyclopropanecarboxylic acid was converted into 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one, then, a 28% sodium hydroxide aqueous solution was dropped to adjust pH of the solution to 7. An extraction operation was repeated three times from this solution with 17.1 kg of toluene, and the resultant three toluene solutions were combined, to obtain 55.7 kg of a toluene solution containing 4.05 kg of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one (32.1 mol, yield based on ethyl cis-3-acetoxymethyl-2,2-dimethylcyclopropanecarboxylate: 96.7%). In this toluene solution, trans-3-hydroxymethyl-2,2-dimethylcyclopropanecarboxylic acid was not detected.

Provenance & Evidence