Dimethylformamide → 2-Bromo-3-fluoro-5-(trifluoromethyl)pyridine
Reaction equation
[F:1][C:2]1[C:3](O)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.P(Br)(Br)([Br:15])=O.CN(C)C=O.C(=O)(O)[O-].[Na+]>>[Br:15][C:3]1[C:2]([F:1])=[CH:7][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:5][N:4]=1Participants
5
Conditions
- Temperature
- 130 °C
Procedure
A mixture of 3-fluoro-5-(trifluoromethyl)pyridin-2-ol (1.0 g, 5.5 mmol, Matrix) and phosphoric tribromide (1.6 g, 5.5 mmol) in N,N-dimethylformamide (2.9 mL, 38 mmol) was heated to 130° C. for 70 minutes. After cooling to room temperature, the mixture was poured onto a mixture of ice and sodium bicarbonate solution (final pH=8). The product was extracted with diethyl ether. The extract was washed with water (twice), followed by brine, dried and solvent removed in vacuo. Flash chromatography, eluting with a gradient from 0-10% ethyl acetate in hexanes afforded product as a colorless oil (0.59 g, 44%). 1H NMR (400 MHz, CDCl3): δ 8.53-8.50 (m, 1H), 7.66 (dd, 1H).
Workup
- temperatureAfter cooling to room temperature
- extractionThe product was extracted with diethyl ether
- washThe extract was washed with water (twice),
- customdried
- customsolvent removed in vacuo
- washFlash chromatography, eluting with a gradient from 0-10% ethyl acetate in hexanes afforded product as a colorless oil (0.59 g, 44%)
Sources & evidence
- ORD record
- ord-06cc5539a08c46f2a6f2699520c22580
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08933085B2
Reaction notes
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