3-Hydroxybenzyl alcohol → 3-(2-Propyn-1-yloxy)benzenemethanol

HRID 1192740Notes

Reaction equation

HRID 1192740 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].C[O-].[Na+].[CH2:13](Cl)[C:14]#[CH:15]>CO.C(Cl)Cl>[CH2:15]([O:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6])[C:14]#[CH:13]

Participants

6

Reactant 3

HCID 1023-Hydroxybenzyl alcoholHCID 122213-Chloro-1-propyneHCID 10942334Sodium Methoxide

Product 1

HCID 107970673-(2-Propyn-1-yloxy)benzenemethanolYield 60%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A 20.0 L flange flask was charged with 3-hydroxybenzyl alcohol (97%, ex. Aldrich, 903 g, 7.28 mol, 1 eq.) in methanol (MeOH)(9.1 L, dried over 3 A molecular sieves) to give a clear solution, into which sodium methoxide (25% in methanol, ex. Aldrich, 1.746 L, 7.63 mol, 1.05 eq.) was slowly added with vigorous stirring. After stirring for 10 min. the propargyl chloride (70 wt % in toluene, ex. Aldrich, 542.6 g, 805 ml, 7.29 mol, 1 eq) was added slowly with vigorous stirring over a period of 30 minutes. The reaction mixture was heated under reflux for 40 h (isomantle set to 76° C. with an internal temp. of 64° C.). TLC-examination (10% MeOH in DCM) showed that the reaction was not complete. The reaction was nevertheless worked-up at this stage. The MeOH was removed by rotary evaporation, and the residue dissolved in DCM (10.2 L) to give a clear solution, which was washed with water (5.82 L×3), and dried over sodium sulfate. The solvent was removed in vacuo, to give the title compound (706 g, 60%) as an orange gum.

Workup

  1. customdried over 3 A molecular sieves)
  2. customto give a clear solution
  3. additionwas added slowly
  4. temperatureThe reaction mixture was heated
  5. temperatureunder reflux for 40 h (isomantle
  6. customset to 76° C. with an internal temp
  7. customof 64° C.
  8. customThe MeOH was removed by rotary evaporation
  9. dissolutionthe residue dissolved in DCM (10.2 L)
  10. customto give a clear solution, which
  11. washwas washed with water (5.82 L×3)
  12. dry with materialdried over sodium sulfate
  13. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-ee0590c068744ee8af4566d81bfc9896
Source dataset
uspto-grants-2014_03
Patent number
US08680265B2

Reaction notes

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