4-Methoxybenzyl alcohol → 2,3-Epoxypropyl-4-methoxybenzyl ether

HRID 1904404Notes

Reaction equation

HRID 1904404 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][OH:8])=[CH:5][CH:4]=1.[H-].[Na+].[H][H].[CH2:15]([CH:17]1[O:19][CH2:18]1)Br>O1CCCC1>[O:19]1[CH2:18][CH:17]1[CH2:15][CH:7]([O:8][CH:7]([CH2:15][CH:17]1[O:19][CH2:18]1)[C:6]1[CH:9]=[CH:10][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[C:6]1[CH:9]=[CH:10][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1

Participants

6

Reactant 4

HCID 77384-Methoxybenzyl alcoholHCID 18430EpibromohydrinHCID 24758Sodium hydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 566290762,3-Epoxypropyl-4-methoxybenzyl ether

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-methoxybenzyl alcohol (800 g, 5.8 mol) in dry tetrahydrofuran (1200 ml) was added dropwise to a stirred slurry of sodium hydride (280 g of a 60% dispersion in oil, 7.0 mol) in dry tetrahydrofuran (600 ml) at -5° C. and under a gentle stream of dry nitrogen. The resulting slurry was allowed to warm up to room temperature and stirred until hydrogen evolution ceased. The resulting slurry containing sodium alkoxide was cooled to -5° C., and treated with epibromohydrin (860 g, 6.3 mol) at a rate so as to maintain the temperature of the reaction mixture below 5° C. The reaction mixture was allowed to warm gradually to room temperature and was stirred for an additional 12 hours. The reaction mixture was filtered and washed with methanol. The filtrate and washings were combined and evaporated to dryness under reduced pressure to yield a crude product (250 g). The crude product was purified by column chromatography (silica gel, chloroform) to yield 2,3-epoxypropyl-4-methoxybenzyl ether as a pale yellow oil having the following structural characteristics:

Workup

  1. temperaturewas cooled to -5° C.
  2. temperatureto maintain the temperature of the reaction mixture below 5° C
  3. temperatureto warm gradually to room temperature
  4. filtrationThe reaction mixture was filtered
  5. washwashed with methanol
  6. customevaporated to dryness under reduced pressure
  7. customto yield a crude product (250 g)
  8. customThe crude product was purified by column chromatography (silica gel, chloroform)

Sources & evidence

ORD record
ord-8b16f27af2c74ca7b14703810db85acc
Source dataset
uspto-grants-1989_06
Patent number
US04837333

Reaction notes

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