Hexane → 1-(2-Methoxyphenyl)-1-(6-methoxy-3-pyridyl)-methanol

HRID 35282

Reaction equation

HRID 35282 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C([Li])CCC.CCCCCC.[CH3:21][O:22][C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH:25]=[O:26]>O1CCCC1>[CH3:21][O:22][C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH:25]([C:2]1[CH:7]=[N:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1)[OH:26]

Participants

6

Reactant 4

HCID 8058HexaneHCID 86582-MethoxybenzaldehydeHCID 27348955-Bromo-2-methoxypyridineHCID 178418339Butyllithium

Product 1

HCID 146734391-(2-Methoxyphenyl)-1-(6-methoxy-3-pyridyl)-methanolYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

5-Bromo-2-methoxypyridine (41.36 g) (prepared by the method of I. Kompis et al, European Journal of Medicinal Chemistry 1977, 12, 531) in dry tetrahydrofuran (50 ml) was cooled to -85° with stirring under a nitrogen atmosphere. n-Butyl lithium (137 ml of a 1.6M hexane solution) in dry tetrahydrofuran (50 ml) was added dropwise, keeping the temperature below -80°. After stirring for 5 minutes, 2-methoxybenzaldehyde (25.0 g) in dry tetrahydrofuran (150 ml) was added dropwise with stirring, keeping the temperature below -70°. The mixture was stirred whilst allowing to warm to room temperature, then quenched with saturated ammonium chloride solution (150 ml). The organic layer was separated and the aqueous was further extracted with ethyl acetate. The organic layers were combined, dried with anhydrous magnesium sulphate and evaporated to dryness to give an orange gum which was crystallised from dichloromethane/petroleum spirit (60-80°) to give 1-(2-methoxyphenyl)-1-(6-methoxy-3-pyridyl)-methanol as a pale yellow solid (28.39 g, 63%) m.p. 83-84°.

Workup

  1. customthe temperature below -80°
  2. stirringAfter stirring for 5 minutes
  3. stirringwith stirring
  4. customthe temperature below -70°
  5. stirringThe mixture was stirred
  6. customquenched with saturated ammonium chloride solution (150 ml)
  7. customThe organic layer was separated
  8. extractionthe aqueous was further extracted with ethyl acetate
  9. dry with materialdried with anhydrous magnesium sulphate
  10. customevaporated to dryness
  11. customto give an orange gum which
  12. customwas crystallised from dichloromethane/petroleum spirit (60-80°)

Sources & evidence

ORD record
ord-de6edea7767d4aee8d0af5865f880d0c
Source dataset
uspto-grants-1988_08
Patent number
US04766121

Linked notes

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