Carbon Dioxide → 3-Isobutoxy-5-methyl-isoxazole-4-carboxylic acid

Temperature

0 °C

To a stirred solution of 4-iodo-3-isobutoxy-5-methyl-isoxazole (669 mg, 2.38) in THF (10 mL) at −30° C. and under argon was added isopropylmagnesium bromide (1.49 mL of a 2.0 M solution in THF) dropwise. The reaction mixture was warmed to 0° C. and stirred for 1 h, then 1,3,5-trioxane (429 mg, 4.76 mmol) in THF (1 mL) was added and the reaction mixture warmed to 50° C. After 1.5 h to the reaction mixture was added further 1,3,5-trioxane (860 mg, 9.52 mmol) and the reaction mixture heated at 70° C. After 2 h the mixture was cooled to 0° C. and solid CO2 (˜10 g) added. After 1 h the reaction mixture was diluted with water (15 mL) then extracted with diethylether. The aqueous phase was acidified with HCl (1 N, 10 mL), then the resultant precipitate filtered off and washed with water (5 mL), then dried under vacuum (60° C.) to afford the title compound (152 mg, 32%) as a white solid. MS: m/e=198.4 [M−H]−.

1. temperaturethe reaction mixture warmed to 50° C
2. temperaturethe reaction mixture heated at 70° C
3. temperatureAfter 2 h the mixture was cooled to 0° C.
4. extractionthen extracted with diethylether
5. filtrationthe resultant precipitate filtered off
6. washwashed with water (5 mL)
7. customdried under vacuum (60° C.)

ORD record

ord-645bcfc8a51546dab68eb819d2704c22

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08357703B2