Sodium Carbonate → 4-[4-Fluoro-3-(trifluoromethyl)phenyl]pyridine

HRID 1005800Notes

Reaction equation

HRID 1005800 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.Br[C:11]1[CH:12]=[CH:13][C:14]([F:21])=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CC.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:21][C:14]1[CH:13]=[CH:12][C:11]([C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)=[CH:16][C:15]=1[C:17]([F:18])([F:19])[F:20]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 27363255-Bromo-2-fluorobenzotrifluoride

Product 1

HCID 219067584-[4-Fluoro-3-(trifluoromethyl)phenyl]pyridineYield 54%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 10311-PropanolSolvent

Procedure

First, 4-(4-fluoro-3-trifluoromethyl-phenyl)-pyridine 73 was prepared as follows. To a suspension of pyridine-4-boronic acid (2.59 g, 21.1 mmol) in 1-propanol (60 mL) was added 5-bromo-2-fluorobenzotrifluoride (5.12 g, 21.1 mmol) and triphenylphosphine (0.160 g, 0.610 mmol), followed by sodium carbonate in water (2.0 M, 12 mL). The mixture was purged with nitrogen gas for 10 minutes. To it was added palladium(II) acetate (0.044 g, 0.196 mmol) and it was then heated under reflux for 4 hours. The reaction mixture was partitioned between ethyl acetate (200 mL) and water (200 mL). The organic layer was separated, washed with brine (3×200 mL), dried over MgSO4, then filtered. After evaporating the solvent, the crude material was loaded to a silica gel column, eluting with 60% ethyl acetate in hexane to give a white solid 73 (2.73 g, 54%). 1H-NMR (CDCl3, 400 MHz) δ 7.34-7.42 (m, 1H), 7.61-7.65 (m, 2H), 7.80-7.93 (m, 2H), 8.73-8.84 (m, 2H); MS (DCI) m/z 242, 243 (M+H)+.

Workup

  1. customFirst, 4-(4-fluoro-3-trifluoromethyl-phenyl)-pyridine 73 was prepared
  2. customThe mixture was purged with nitrogen gas for 10 minutes
  3. temperaturewas then heated
  4. temperatureunder reflux for 4 hours
  5. customThe reaction mixture was partitioned between ethyl acetate (200 mL) and water (200 mL)
  6. customThe organic layer was separated
  7. washwashed with brine (3×200 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customAfter evaporating the solvent
  11. washeluting with 60% ethyl acetate in hexane

Sources & evidence

ORD record
ord-4567dd05ee794e399c74b2266ead8d3c
Source dataset
uspto-grants-2004_09
Patent number
US06787542B2

Reaction notes

Loading…