Cesium carbonate → 5-Ethenyl-2-(trifluoromethyl)pyridine

HRID 2176136Notes

Reaction equation

HRID 2176136 reaction equation
[CH:1]([B-](F)(F)F)=[CH2:2].[K+].Br[C:9]1[CH:10]=[CH:11][C:12]([C:15]([F:18])([F:17])[F:16])=[N:13][CH:14]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.[Pd](Cl)Cl.O1CCCC1>[F:16][C:15]([F:18])([F:17])[C:12]1[CH:11]=[CH:10][C:9]([CH:1]=[CH2:2])=[CH:14][N:13]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 27611975-Bromo-2-(trifluoromethyl)pyridineHCID 23679353Potassium vinyltrifluoroborate

Product 1

HCID 574168485-Ethenyl-2-(trifluoromethyl)pyridine

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
77.5 °C

Procedure

Potassium vinyltrifluoroborate (362 mg, 2.7 mmol; Aldrich), 5-bromo-2-trifluoromethylpyridine (539 mg, 2.38 mmol; Aldrich) and triphenylphosphine (37.7 mg, 0.144 mmol) were added at room temperature to a solution of cesium carbonate (2.16 g, 6.63 mmol) in water (2 mL). Tetrahydrofuran (18 mL) was added, and the reaction flask was evacuated and purged with nitrogen (3 cycles). Palladium(II) chloride (9.2 mg, 0.052 mmol) was added, and the reaction flask was again evacuated and purged with nitrogen (3 cycles), then heated under nitrogen at 75-80° C. for 22 hours. The mixture was cooled to room temperature and the aqueous layer was separated and extracted with ethyl ether (2×5 mL). The combined organic phase was concentrated by distillation through a Vigreaux column at atmospheric pressure to a volume of approximately 2 mL, and the residue was purified by flash chromatography (40 g silica, eluted with hexanes-ethyl acetate, 100:0-90:10). The product-containing fractions were combined and concentrated by distillation through a Vigreaux column at atmospheric pressure to a volume of approximately 2 mL, then distilled bulb-to-bulb (air bath 80-90° C./10-20 torr) to provide the title compound: 1H NMR (300 MHz, methanol-d4) δ 5.56 (d, J=10.9 Hz, 1H), 6.08 (d, J=17.6 Hz, 1H), 6.86 (dd, J=17.8, 11.0 Hz, 1H), 7.77 (d, J=8.1 Hz, 1H), 8.11 (dd, J=8.3, 2.2 Hz, 1H), 8.74 ppm (d, J=1.7 Hz, 1H).

Workup

  1. customthe reaction flask was evacuated
  2. custompurged with nitrogen (3 cycles)
  3. customthe reaction flask was again evacuated
  4. custompurged with nitrogen (3 cycles)
  5. temperatureThe mixture was cooled to room temperature
  6. customthe aqueous layer was separated
  7. extractionextracted with ethyl ether (2×5 mL)
  8. concentrationThe combined organic phase was concentrated by distillation through a Vigreaux column at atmospheric pressure to a volume of approximately 2 mL
  9. customthe residue was purified by flash chromatography (40 g silica, eluted with hexanes-ethyl acetate, 100:0-90:10)
  10. concentrationconcentrated by distillation through a Vigreaux column at atmospheric pressure to a volume of approximately 2 mL
  11. distillationdistilled bulb-to-bulb (air bath 80-90° C./10-20 torr)

Sources & evidence

ORD record
ord-f5f2ee1b5e5646de9df5f974ea43e0e3
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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