Carbon Dioxide → 3-(2-Formylphenyl)benzo[d]isoxazole-6-carboxylic acid

Participants

Reaction Steps

To a solution of 6-bromo-3-(2-(diethoxymethyl)phenyl)benzo[d]isoxazole (Compound 5) (50 g) in dry ether (330 mL) under nitrogen at −78° C. was added a 2.5M solution of n-butyl lithium in hexanes (55.8 mL) was added dropwise and stirring continued at −78° C. for 45 min. The thick brown suspension was transferred via cannula to a mechanically stirred mixture of solid carbon dioxide pellets in ether (250 mL, under nitrogen and cooled in acetone/dry ice bath) and the resulting reaction mix topped up with further carbon dioxide pellets and left stirring in cold bath under nitrogen whilst warming to room temperature overnight. The reaction was quenched with 2N HCl (100 mL) and the ether removed under reduced pressure and ethanol (300 mL) added. The resultant yellow suspension was stirred on at 60° C. for 15 min, then cooled to room temperature and stirred in ice bath for 30 min and resulting yellow solid isolated by filtration and dried in vacuum oven at 45° C. to give the title product (29.76 g).

Provenance & Evidence