Boron Trichloride → Ver-50589

Temperature

0 °C

To an ice-bath cooled solution of 5-(2,4-Bis-benzyloxy-5-chlorophenyl)-4-(4-methoxy-phenyl)-isoxazole-3-carboxylic acid ethylamide (0.213 mg, 0.374 mmol) in dichloromethane (5 mL) under a nitrogen atmosphere was added a 1.0M solution of Boron trichloride in dichloromethane (1.12 mL; 1.12 mmol). The reaction mixture was stirred at 0° C. for 15 minutes then at ambient temperature for 35 minutes. The reaction mixture was re-cooled to 0° C. and quenched by the addition of saturated aqueous sodium hydrogen carbonate solution (5 mL). After stirring for 5 minutes the dichloromethane was removed in vacuo and the residue was partitioned between ethyl acetate (30 mL) and water (30 mL). The phases were separated and the organic phase was washed with water (30 mL), saturated aqueous sodium chloride solution (30 mL) then dried over sodium sulphate. The mixture was filtered and the filtrate solvents were removed in vacuo to afford a foam-like colourless solid which was purified by adsorption onto silica gel then flash chromatography on silica gel (10 g IST) eluting with 50% ethyl acetate in hexane. This affords 5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxy-phenyl)-isoxazole-3-carboxylic acid ethylamide as a colourless solid (0.097 g; 67%). LCMS: [M+H]+ 391, 389 (37Cl; 35Cl). 1H NMR (400 MHz, d6-DMSO) □ 1.08 (t, 3H), 3.22 (m, 2H), 3.73 (s, 3H), 6.59 (s 1H), 6.87 (d, 1H), 7.13-7.17 (m, 3H), 8.88 (br t, 1H), 10.09 (s, 1H), 10.62 (s, 1H).

1. waitat ambient temperature for 35 minutes
2. temperatureThe reaction mixture was re-cooled to 0° C.
3. customquenched by the addition of saturated aqueous sodium hydrogen carbonate solution (5 mL)
4. stirringAfter stirring for 5 minutes the dichloromethane
5. customwas removed in vacuo
6. customthe residue was partitioned between ethyl acetate (30 mL) and water (30 mL)
7. customThe phases were separated
8. washthe organic phase was washed with water (30 mL), saturated aqueous sodium chloride solution (30 mL)
9. dry with materialthen dried over sodium sulphate
10. filtrationThe mixture was filtered
11. customthe filtrate solvents were removed in vacuo
12. customto afford a foam-like colourless solid which
13. customwas purified by adsorption onto silica gel
14. washflash chromatography on silica gel (10 g IST) eluting with 50% ethyl acetate in hexane

ORD record

ord-9b0e14ec528b443a8b21cf073feda7a4

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450310B2