Chloromethyl Methyl Ether → [5-(Methoxymethoxy)-2-methyl-phenyl]methanol

HRID 527634Notes

Reaction equation

HRID 527634 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[H-].[Na+].Cl[CH2:15][O:16][CH3:17].[H-].[H-].[H-].[H-].[Li+].[Al+3]>O1CCCC1.C(OCC)(=O)C>[CH3:15][O:16][CH2:17][O:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:11])=[C:6]([CH2:7][OH:9])[CH:10]=1

Participants

7

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 2351885-Hydroxy-2-methylbenzoic acidHCID 21226445Aluminium lithium hydride

Product 1

HCID 67966822[5-(Methoxymethoxy)-2-methyl-phenyl]methanolYield 78.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

5-Hydroxy-2-methyl-benzoic acid (2 g, 13.3 mmol) was dissolved in tetrahydrofuran (40 ml). The reaction mixture was cooled to 0° C. and sodium hydride (60% dispersion in mineral oil) (1.8 g, 39.5 mmol) was added portionwise. Chloro(methyloxy)methane (4 ml, 52 mmol) was added. The reaction mixture was stirred for 30 min at 0° C. The mixture was poured into ice and extracted with ethyl acetate, two phases were separated and the organic layer was dried over Na2SO4 and evaporated under vacuum to give the crude product as a yellow oil. To this material, dissolved in THF (20 ml), cooled at 0° C., LiAlH4 1M in THF (15 ml, 15 mmol) was added dropwise and the reaction mixture was stirred at 0° C. for 30 min. After this time the reaction mixture was poured into ice and diluted with 60 ml of ethyl acetate. Phases were separated, the organic phase was dried over Na2SO4 and evaporated under vacuum to afford a colorless oil that was purified by flash chromatography (Biotage system) on silica gel using a 100 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 75:25 as eluents affording the title compound (1.9 g) as a colorless oil.

Workup

  1. additionThe mixture was poured into ice
  2. extractionextracted with ethyl acetate, two phases
  3. customwere separated
  4. dry with materialthe organic layer was dried over Na2SO4
  5. customevaporated under vacuum
  6. customto give the crude product as a yellow oil
  7. temperaturecooled at 0° C.
  8. stirringthe reaction mixture was stirred at 0° C. for 30 min
  9. additionAfter this time the reaction mixture was poured into ice
  10. customPhases were separated
  11. dry with materialthe organic phase was dried over Na2SO4
  12. customevaporated under vacuum
  13. customto afford a colorless oil that
  14. customwas purified by flash chromatography (Biotage system) on silica gel using a 100 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 75:25 as eluents

Sources & evidence

ORD record
ord-3207b0d6735b49cd901c86cb67f39dcf
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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