Carbon tetrabromide → 3-(2,2-Dibromovinyl)-5-phenyl-4-(trifluoromethyl)isoxazole

Temperature

0 °C

To a solution of carbon tetrabromide (12.24 g, 36.9 mmol) in dichloromethane (10 mL) at 0° C. was added a solution of triphenylphosphine (4.84 g, 18.5 mmol) in dichloromethane (10 mL), and the resulting mixture was stirred at 0° C. for 5 min. A solution of 5-phenyl-4-(trifluoromethyl)isoxazole-3-carbaldehyde (Intermediate I-13B, 1.59 g, 4.62 mmol) in dichloromethane (10 mL) was added via syringe, and the reaction mixture was stirred at 0° C. for 20 min. The reaction mixture was diluted with dichloromethane and washed with water. A white precipitate formed in the organic and was removed by vacuum filtrating. The filtrate was washed with a saturated aqueous solution of sodium bicarbonate, washed with a saturated aqueous solution of ammonium chloride, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash silica gel chromatography using a mixture of ethyl acetate in hexane (1%-3%) to give 3-(2,2-dibromovinyl)-5-phenyl-4-(trifluoromethyl)isoxazole (1.21 g, 3.05 mmol, 66.0% yield) as a white solid. The product had an HPLC ret. time=3.10 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=397.9. 1H NMR (500 MHz, CDCl3) δ ppm 7.43 (s, 1H), 7.52-7.56 (m, 2H), 7.56-7.61 (m, 1H), and 7.74 (d, J=7.49 Hz, 2H).

1. stirringthe reaction mixture was stirred at 0° C. for 20 min
2. washwashed with water
3. customA white precipitate formed in the organic and
4. customwas removed by vacuum
5. filtrationfiltrating
6. washThe filtrate was washed with a saturated aqueous solution of sodium bicarbonate
7. washwashed with a saturated aqueous solution of ammonium chloride
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated
10. customThe residue was purified by flash silica gel chromatography
11. additiona mixture of ethyl acetate in hexane (1%-3%)

ORD record

ord-df8d7c47980f4128a714e4f7e21456e9

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216972B2