Vinyl Acetate → (1R)-1-(Pyridin-2-yl)ethan-1-ol

HRID 911441Notes

Reaction equation

HRID 911441 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]([OH:9])[CH3:8].C(OC=C)(=O)C.N1C=CC=CC=1[C@H](OC(=O)C)C.C(=O)([O-])[O-].[K+].[K+]>O(C(C)C)C(C)C.CO.O.[Cl-].[Na+].O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C@H:7]([OH:9])[CH3:8]

Participants

9

Reactant 4

HCID 7904Vinyl AcetateHCID 11430Potassium CarbonateHCID 86784alpha-Methyl-2-pyridinemethanolHCID 13138793HCID 13138793, compound

Product 1

HCID 642847(1R)-1-(Pyridin-2-yl)ethan-1-olYield 89%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 7914Diisopropyl EtherSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Stir a mixture of (±)-1-(pyridin-2-yl)-ethanol (21.2 mmol), 4 A molecular sieves powder (3 g), vinyl acetate (6 mL) and lipase Candida Antarctica acrylic resin (0.87 g) in i-Pr2O (40 mL) at ambient temperature overnight-(J. Org. Chem. 1998, 63, 2481-2487; Synlett 1999, 41-44). Remove the solid residue by filtration. Evaporate the volatile substances and purify by chromatography eluting with hexane/EtOAc (7:3 to 1:1) to give the faster eluting (R)acetic acid 1-(pyridin-2-yl)-ethyl ester as colorless oil (50%) and the slower eluting (S)-alcohol as light yellow oil (43%). Dissolve (R)-acetic acid 1-(pyridin-2-yl)-ethyl ester (9.620 mmol) in methanol (50 mL) and add potassium carbonate (38.48 mmol) in water (10 mL). Stir the mixture at ambient temperature for 4 h. Dilute with brine, extract three times with EtOAc, dry over anhydrous Na2SO4, filter through a short pad of silica gel and concentrate in vacuo to give the desired intermediate as a colorless oil (89%).

Workup

  1. customRemove the solid residue
  2. filtrationby filtration
  3. customEvaporate the volatile substances
  4. custompurify by chromatography
  5. washeluting with hexane/EtOAc (7:3 to 1:1)
  6. customto give the
  7. washfaster eluting (R)acetic acid 1-(pyridin-2-yl)-ethyl ester as colorless oil (50%)
  8. washthe slower eluting (S)-alcohol as light yellow oil (43%)
  9. stirringStir the mixture at ambient temperature for 4 h
  10. extractionextract three times with EtOAc
  11. dry with materialdry over anhydrous Na2SO4
  12. filtrationfilter through a short pad of silica gel
  13. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-25c25f32dc544346857b1ad1b5562bf3
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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