Hydrochloric Acid → 1-Benzyl-3,3-difluoropiperidine-4,4-diol

HRID 2206263Notes

Reaction equation

HRID 2206263 reaction equation
[CH2:1]([N:8]1[CH2:13][C:12]([F:15])([F:14])[C:11]([OH:16])=[C:10](C(OCC)=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[O:23]1CCOCC1>>[CH2:1]([N:8]1[CH2:9][CH2:10][C:11]([OH:16])([OH:23])[C:12]([F:14])([F:15])[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 67343743Ethyl 1-benzyl-5,5-difluoro-4-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylate

Product 1

HCID 574158661-Benzyl-3,3-difluoropiperidine-4,4-diol

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 1-benzyl-5,5-difluoro-4-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylate (5.0 g) and conc. hydrochloric acid (40 mL) in 1,4-dioxane (15 mL) was stirred at 80° C. for 3 hr. The reaction mixture was concentrated under reduced pressure, and diluted with ethyl acetate, and the mixture was adjusted to pH-9 with saturated aqueous sodium carbonate solution. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was washed with dichloromethane to give the title compound (1.40 g).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. washThe residue was washed with dichloromethane

Sources & evidence

ORD record
ord-269f23fdeb6f4e689d03b04e158a7fcd
Source dataset
uspto-grants-2016_06
Patent number
US09371320B2

Reaction notes

Loading…