Sodium Hydroxide → 1-(4-Bromo-3-methylisoxazol-5-yl)cyclopropane-1-carboxylic acid

Temperature

45 °C

To a solution of ethyl 1-(4-bromo-3-methylisoxazol-5-yl)cyclopropanecarboxylate (11.8 g, 43.0 mmol) in THF (60 mL) was added aqueous NaOH (86 mL, 86 mmol, 1 M). The dark brown bi-phasic reaction mixture was vigorously stirred and heated to 45° C. until consumption of SM (3-4 h) was detected by LC-MS and TLC analysis. After 4 h, the homogeneous mixture was cooled to room temperature and diluted with hexanes. The organic phase was separated and the aqueous phase (pH ˜14) was acidified with aqueous 1 N HCl (pH 1) (˜100 mL). The product crystallizes upon acidification of the aqueous layer. After vigorously stirring for 30 min, the solids were filtered, washed with cold (0° C.) water (3×50 mL), and dried to give white crystals. The product 1-(4-bromo-3-methylisoxazol-5-yl)cyclopropanecarboxylic acid (10.0 g, 40.6 mmol, 94% yield) was isolated as white crystals. LC/MS m/z 246 [M+H]+.

1. temperaturethe homogeneous mixture was cooled to room temperature
2. customThe organic phase was separated
3. customThe product crystallizes upon acidification of the aqueous layer
4. stirringAfter vigorously stirring for 30 min
5. filtrationthe solids were filtered
6. washwashed with cold (0° C.) water (3×50 mL)
7. customdried
8. customto give white crystals

ORD record

ord-6af3f56aa6c6420d86f4410042ba16e6

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796261B2