Sodium borohydride → 2-Fluoro-5-(1-(4-(methylthio)phenyl)ethyl)pyridine

HRID 1811998Notes

Reaction equation

HRID 1811998 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([S:16][CH3:17])=[CH:12][CH:11]=2)=[CH2:9])=[CH:4][N:3]=1.[BH4-].[Na+]>C1COCC1.O.C(Cl)Cl.O.[Ru](Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[CH:11]=[CH:12][C:13]([S:16][CH3:17])=[CH:14][CH:15]=2)[CH3:9])=[CH:4][N:3]=1

Participants

7

Reactant 2

HCID 4311764Sodium borohydride3×HCID 666002122-Fluoro-5-(1-(4-(methylthio)phenyl)vinyl)pyridine

Product 1

HCID 665999572-Fluoro-5-(1-(4-(methylthio)phenyl)ethyl)pyridineYield 87.6%

Reagents, catalysts & solvents 4

HCID 6093376Ruthenium trichloride hydrateCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

2-Fluoro-5-(1-(4-(methylthio)phenyl)vinyl)pyridine (992 mg, 4.04 mmol) was dissolved in THF (12 mL) and water (4 mL) and the flask was cooled in an ice water bath under nitrogen. Then, ruthenium trichloride hydrate (212.4 mg, 0.9422 mmol) was added, and then sodium borohydride (393 mg, 10.4 mmol) was added portionwise over about 5 min. More THF (2 mL) was added, and the reaction was warmed to room temperature and stirred. After 2 hours and 15 minutes, more RuCl3*H2O (214 mg, 0.951 mmol) was added and the flask was again cooled in an ice water bath. Then, more sodium borohydride (384 mg, 10.2 mmol) was added, and the reaction was warmed to room temperature. The stirring was continued. Gas evolution was observed. After 50 min, more sodium borohydride (139 mg, 3.67 mmol) was added, and stirring was continued for 1 h. The reaction was diluted with water (20 mL) and DCM (30 mL). The suspension was filtered through a Celite® (diatomaceous earth) pad, which was washed repeatedly with DCM. The biphasic mixture was treated with saturated sodium bicarbonate (50 mL), and the layers were separated. The aqueous phase was extracted with DCM, and all the organic phases were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (150 mL fritted funnel with about 2 inches of silica gel; DCM) to give 2-fluoro-5-(1-(4-(methylthio)phenyl)ethyl)pyridine (875 mg). 1H NMR (CDCl3, 400 MHz) δ 8.10 (d, J=1.96 Hz, 1H), 7.56 (td, J=8.07 Hz, 2.64 Hz, 1H), 7.24-7.19 (m, 2H), 7.15-7.09 (m, 2H), 6.84 (dd, J=8.41 Hz, 2.93 Hz, 1H), 4.15 (q, J=7.24 Hz, 1H), 2.47 (s, 3H), 1.64 (d, J=7.24 Hz, 3H). m/z (ESI, pos. ion) 248 (M+H)+.

Workup

  1. temperaturethe flask was again cooled in an ice water bath
  2. temperaturethe reaction was warmed to room temperature
  3. waitAfter 50 min
  4. stirringstirring
  5. waitwas continued for 1 h
  6. filtrationThe suspension was filtered through a Celite® (diatomaceous earth) pad, which
  7. washwas washed repeatedly with DCM
  8. additionThe biphasic mixture was treated with saturated sodium bicarbonate (50 mL)
  9. customthe layers were separated
  10. extractionThe aqueous phase was extracted with DCM
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. custompurified on a silica gel
  15. filtrationfilter (150 mL fritted funnel with about 2 inches of silica gel; DCM)

Sources & evidence

ORD record
ord-e2dddd489bbd4d7ab00fe488cae18c8a
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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