Azobisisobutyronitrile → {4-[5-(4-Fluoro-2-methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-3-phenyl-isoxazol-5-yl}-methanol

Temperature

70 °C

To a solution of 2-(4-fluoro-2-methoxy-phenyl)-5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazole (1.95 g, 5.56 mmol) in carbon tetrachloride (20 mL) was added N-bromo succinimide (990 mg, 5.56 mmol) and 2,2′-azobis(2-methylpropionitrile) (46 mg, 0.28 mmol) and the reaction mixture was stirred for 4 h at 70° C. Further 2,2′-azobis(2-methylpropionitrile) (46 mg, 0.28 mmol) was added and stirring was continued for another 14 h at 70° C. N-Bromo succinimide (378 mg, 2.12 mmol) was added and the mixture stirred for another 4 h at 90° C. After the reaction mixture was cooled to 0° C. the suspension was filtered off and was washed with dichloromethane (30 mL 1) and aqueous sodium hydrogencarbonate (1 N). It was extracted with dichloroemthane and dried over sodium sulfate resulting in crude material (1.66 g). A part of this light brown solid (200 mg) was suspended in water (0.5 mL) and DMSO (2.0 mL) and the reaction mixture was stirred for 18 h at 60° C. the resulting solution was diluted with ethyl acetate (10 mL) and washed with water (10 mL) and brine (10 mL). The aqueous layers were extracted with ethyl acetate. Drying over sodium sulfate and urification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=70:10:20 to 20:60:20) afforded the title compound (57 mg, 33%) as a white solid. MS: m/e=368.1 [M+H]+.

1. stirringstirring
2. waitwas continued for another 14 h at 70° C
3. stirringthe mixture stirred for another 4 h at 90° C
4. temperatureAfter the reaction mixture was cooled to 0° C. the suspension
5. filtrationwas filtered off
6. washwas washed with dichloromethane (30 mL 1) and aqueous sodium hydrogencarbonate (1 N)
7. extractionIt was extracted with dichloroemthane
8. dry with materialdried over sodium sulfate resulting in crude material (1.66 g)
9. stirringDMSO (2.0 mL) and the reaction mixture was stirred for 18 h at 60° C. the resulting solution
10. additionwas diluted with ethyl acetate (10 mL)
11. washwashed with water (10 mL) and brine (10 mL)
12. extractionThe aqueous layers were extracted with ethyl acetate
13. dry with materialDrying over sodium sulfate and urification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=70:10:20 to 20:60:20)

ORD record

ord-ca0be20c949d4dc9876eae165fc78f24

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07956074B2