Ethyl Acetate → 2-(4-fluorotetrahydro-2H-pyran-4-yl)-2-hydroxyacetonitrile

HRID 20386

Reaction equation

HRID 20386 reaction equation
[O:1]1[C:3]2([CH2:8][CH2:7][O:6][CH2:5][CH2:4]2)[CH:2]1[C:9]#[N:10].N1C=CC=CC=1.[FH:17].C(OCC)(=O)C>ClCCl>[F:17][C:3]1([CH:2]([OH:1])[C:9]#[N:10])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 64774Pyridine, hydrofluoride (1:1)HCID 214379031,6-Dioxaspiro[2.5]octane-2-carbonitrileHCID 178435178HCID 178435178, compound

Product 1

HCID 866153632-(4-fluorotetrahydro-2H-pyran-4-yl)-2-hydroxyacetonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve 1,6-dioxaspiro[2,5]octane-2-carbonitrile (4.14 g, 29.8 mmol) in dry dichloromethane (10 mL) and cool to 0° C. under a nitrogen atmosphere in a polypropylene bottle. Add hydrogen fluoride-pyridine (3 mL) dropwise. Allow the mixture to slowly warm to room temperature over 3 h and then stir an additional 1.5 hours at room temperature. Pour into ethyl acetate and wash with saturated aqueous sodium bicarbonate solution until washes remain basic. Combine the aqueous washes and adjust the pH of the solution to ˜pH=8 and extract with ethyl acetate. Combine this organic extract with the ethyl acetate solution of the crude reaction mixture and wash with saturated aqueous sodium chloride solution, dry (magnesium sulfate), filter and concentrate to give the desired compound as a yellow oil which is used directly in the next reaction.

Workup

  1. washwash with saturated aqueous sodium bicarbonate solution until washes
  2. extractionextract with ethyl acetate
  3. extractionCombine this organic extract with the ethyl acetate solution of the crude
  4. customreaction mixture
  5. washwash with saturated aqueous sodium chloride solution
  6. dry with materialdry (magnesium sulfate)
  7. filtrationfilter
  8. concentrationconcentrate

Sources & evidence

ORD record
ord-c2ffc7839d594b18a2fa1dae6989220d
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

Loading…