Sodium Chloride → alpha-(3-Methoxypyridin-2-yl)-3-ethoxybenzyl alcohol

HRID 1596409Notes

Reaction equation

HRID 1596409 reaction equation
BrC1C(C)=CC(C)=CC=1C.C([Li])(C)(C)C.[CH3:16][O:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1.[CH2:24]([O:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH:30]=[O:31])[CH3:25].[Cl-].[Na+]>O1CCCC1.CCCCC>[CH3:16][O:17][C:18]1[C:19]([CH:30]([OH:31])[C:29]2[CH:32]=[CH:33][CH:34]=[C:27]([O:26][CH2:24][CH3:25])[CH:28]=2)=[N:20][CH:21]=[CH:22][CH:23]=1

Participants

8

Reactant 5

HCID 5234Sodium Chloride2×HCID 237193-MethoxypyridineHCID 684732-BromomesityleneHCID 899083-EthoxybenzaldehydeHCID 178418306HCID 178418306, compound

Product 1

HCID 53994409alpha-(3-Methoxypyridin-2-yl)-3-ethoxybenzyl alcoholYield 59%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-bromomesitylene (9.16 ml, 60 m mol) in tetrahydrofuran (250 ml), a 1.64 M pentane solution of tert-butyl lithium (73 ml, 120 m mol) was added dropwise at −50° C. or below. After this mixture was stirred for 30 minutes, 3-methoxypyridine (5.0 g, 46 m mol) was added dropwise thereto at −50° C. or below and the resulting mixture was stirred at −20° C. for 2 hours. After the reaction mixture was cooled again to −50° C. or below, 3-ethoxybenzaldehyde (10.3 g, 69 m mol) was added dropwise thereto and the stirring was continued for another 30 minutes. After the addition of a saturated aqueous solution of sodium chloride (10 ml), the reaction mixture was returned to room temperature. After a saturated aqueous solution of sodium chloride (200 ml) was further added thereto, the organic layer was separated. The aqueous layer was extracted with ethyl acetate (200 ml), and the extract was combined with the previous organic layer. After the combined organic layer was washed with a saturated aqueous solution of sodium chloride (50 ml) and dried over magnesium sulfate, the solvent was distilled off under reduced pressure. The resulting solid was washed with hexane and then recrystallized from methanol (300 ml) to obtain the desired compound (7.0 g, 59%) as colorless crystals.

Workup

  1. stirringat −50° C. or below and the resulting mixture was stirred at −20° C. for 2 hours
  2. temperatureAfter the reaction mixture was cooled again to −50° C. or below
  3. waitthe stirring was continued for another 30 minutes
  4. customwas returned to room temperature
  5. customthe organic layer was separated
  6. extractionThe aqueous layer was extracted with ethyl acetate (200 ml)
  7. washAfter the combined organic layer was washed with a saturated aqueous solution of sodium chloride (50 ml)
  8. dry with materialdried over magnesium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. washThe resulting solid was washed with hexane
  11. customrecrystallized from methanol (300 ml)

Sources & evidence

ORD record
ord-4c7723fc232948af9de0b398066f8679
Source dataset
uspto-grants-2001_09
Patent number
US06291485B1

Reaction notes

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