Diethyl Ether → 1-(5-Benzyloxy-2-methoxyphenyl)-1-(6-methoxy-3-pyridyl)methanol

HRID 1165620Notes

Reaction equation

HRID 1165620 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.CCOCC.C([Li])CCC.[CH2:20]([O:27][C:28]1[CH:29]=[CH:30][C:31]([O:36][CH3:37])=[C:32]([CH:35]=1)[CH:33]=[O:34])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O1CCCC1.CCCCCC>[CH2:20]([O:27][C:28]1[CH:29]=[CH:30][C:31]([O:36][CH3:37])=[C:32]([CH:33]([C:2]2[CH:7]=[N:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)[OH:34])[CH:35]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 27348955-Bromo-2-methoxypyridineHCID 109666945-(Benzyloxy)-2-methoxybenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 143331211-(5-Benzyloxy-2-methoxyphenyl)-1-(6-methoxy-3-pyridyl)methanolYield 72.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

5-Bromo-2-methoxypyridine (15.87 g) was dissolved in dry tetrahydrofuran (50 ml) and the solution cooled with mechanccal stirring under nitrogen to -100° (ether/liquid nitrogen). A solution of n-butyl lithium in hexane (53 ml of a 1.6M solution) was added dropwise, maintaining the temperature below -90°; a white precipitate appeared. After 5 minutes, 5-benzyloxy-2-methoxybenzaldehyde (17.04 g) in dry tetrahydrofuran (150 ml) was added dropwise, maintaining the temperature below -95°. After the addition was complete, the mixture was stirred to 5°. The dark solution was quenched with excess saturated ammonium chloride, the organic layer removed, the aqueous extracted with ethyl acetate, then the combined organics dried with anhydrous magnesium sulphate and evaporated. The residue crystallised from ether/petroleum spirit to give 1-(5-benzyloxy-2-methoxyphenyl)-1-(6-methoxy-3-pyridyl)methanol (17.83 g, 72%), m.p. 80°-82°.

Workup

  1. temperaturethe solution cooled
  2. temperaturemaintaining the temperature below -90°
  3. temperaturemaintaining the temperature below -95°
  4. additionAfter the addition
  5. customThe dark solution was quenched with excess saturated ammonium chloride
  6. customthe organic layer removed
  7. extractionthe aqueous extracted with ethyl acetate
  8. dry with materialthe combined organics dried with anhydrous magnesium sulphate
  9. customevaporated
  10. customThe residue crystallised from ether/petroleum spirit

Sources & evidence

ORD record
ord-b8498fe322ce4a8fbd72325b3e81e6f6
Source dataset
uspto-grants-1990_03
Patent number
US04910305

Reaction notes

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