Methyl iodide → 5-(2-Chlorophenyl)-1,2,3,6-tetrahydro-1-methylpyridine

HRID 2245259Notes

Reaction equation

HRID 2245259 reaction equation
Cl[C:2]1C=CC=CC=1B(O)O.BrC1C=NC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=1.IC.[BH4-].[Na+]>C1(C)C=CC=CC=1.ClCCl.CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[Cl:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[CH2:32][N:33]([CH3:2])[CH2:34][CH2:35][CH:36]=1

Participants

12

Reactant 6

HCID 6328Methyl iodideHCID 10340Sodium CarbonateHCID 122863-BromopyridineHCID 27343222-Chlorophenylboronic acidHCID 4311764Sodium borohydrideHCID 109870503-(2-Chlorophenyl)pyridine

Product 1

HCID 684186035-(2-Chlorophenyl)-1,2,3,6-tetrahydro-1-methylpyridineYield 88.8%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-chlorophenylboronic acid (5.0 g), 3-bromopyridine (4.8 g) and tetrakis(triphenylphosphine)palladium(0) (1.0 g) in toluene (47 ml), aqueous 2 M sodium carbonate solution (35 ml) and ethanol (2.4 ml) was heated under reflux for 5.5 h. The reaction mixture was cooled, and the toluene layer was separated. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were dried (MgSO4), filtered, and the filtrate evaporated under reduced pressure to give crude 3-(2-chlorophenyl)pyridine (7.9 g). To a solution of the 3-(2-chlorophenyl)pyridine (7.9 g) in dichloromethane (50 ml) was added iodomethane (3.8 ml) and the mixture was stirred for 15 h. The solvent was evaporated under reduced pressure and the obtained residue was crystallized from ethyl acetate to give a pale-yellow crystal. To a solution of the obtained crystals in methanol (60 ml) was added sodium borohydride (1.7 g) under ice-cooling, and the mixture was stirred at room temperature for 3 h. The mixture was quenched with a saturated aqueous sodium chloride solution. The mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give a crude 5-(2-chlorophenyl)-1,2,3,6-tetrahydro-1-methylpyridine (5.9 g).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 5.5 h
  3. temperatureThe reaction mixture was cooled
  4. customthe toluene layer was separated
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customthe filtrate evaporated under reduced pressure
  9. customto give crude 3-(2-chlorophenyl)pyridine (7.9 g)
  10. customThe solvent was evaporated under reduced pressure
  11. customthe obtained residue was crystallized from ethyl acetate
  12. customto give a pale-yellow crystal
  13. temperaturecooling
  14. stirringthe mixture was stirred at room temperature for 3 h
  15. customThe mixture was quenched with a saturated aqueous sodium chloride solution
  16. extractionThe mixture was extracted with ethyl acetate
  17. washThe extract was washed with a saturated aqueous sodium chloride solution
  18. dry with materialdried over anhydrous magnesium sulfate
  19. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-309f04b9805149f9b22683406185ae2e
Source dataset
uspto-grants-2010_03
Patent number
US07683069B2

Reaction notes

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