Triethylamine → HCID 67121150, compound

To a stirred solution of (4-chloro-5-(3-fluoro-4-(trifluoromethyl)phenyl)isoxazol-3-yl)methanol (580 mg, 1.96 mmol) and triethylamine (1.930 mL, 13.73 mmol) in dichloromethane (9.6 mL) and DMSO (1.60 mL), sulphur trioxide pyridine complex (1.25 g, 7.85 mmol) was added. The reaction mixture was stirred for 2 hours at room temperature before removal of the volatiles in vacuo. The resultant crude residue was diluted with ethylacetate (20 mL), washed with 2N HCl (30 mL), water (30 mL) and brine (30 mL). The organic phase was dried with Na2SO4, filtered and evaporated to dryness in vacuo. This crude mixture was dissolved in tBuOH/H2O (4:1) (20 mL), and to this sodium dihydrogen phosphate dihydrate (1.07 g, 6.87 mmol) and a solution of 2-methyl-2-butene (860 mg, 12.26 mmol) in tetrahydrofuran (5 mL), was added. Finally sodium chlorite (222 mg, 2.45 mmol) was added and the reaction mixture stirred overnight. The reaction mixture was evaporated to dryness, partitioned between ethyl acetate (20 mL) and water (15 mL) and the aqueous phase acidified to pH 4 with acetic acid. The organic layer was removed and then the aqueous layer extracted with ethyl acetate (3×20 mL). The organics were combined, dried with Na2SO4, filtered and evaporated to dryness in vacuo. The resulting residue was purified by silica gel chromatography, eluting with dichloromethane to 20% methanol/(acetic acid) in dichloromethane, to afford 4-chloro-5-(3-fluoro-4-(trifluoromethyl)phenyl)isoxazole-3-carboxylic acid (0.4 g, 1.29 mmol).

1. washwashed with 2N HCl (30 mL), water (30 mL) and brine (30 mL)
2. dry with materialThe organic phase was dried with Na2SO4
3. filtrationfiltered
4. customevaporated to dryness in vacuo
5. dissolutionThis crude mixture was dissolved in tBuOH/H2O (4:1) (20 mL)
6. stirringthe reaction mixture stirred overnight
7. customThe reaction mixture was evaporated to dryness
8. custompartitioned between ethyl acetate (20 mL) and water (15 mL)
9. customThe organic layer was removed
10. extractionthe aqueous layer extracted with ethyl acetate (3×20 mL)
11. dry with materialdried with Na2SO4
12. filtrationfiltered
13. customevaporated to dryness in vacuo
14. customThe resulting residue was purified by silica gel chromatography
15. washeluting with dichloromethane to 20% methanol/(acetic acid) in dichloromethane

ORD record

ord-660403b2ff334a4285cdcf3303c418b6

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08211927B2