Hydrochloric Acid → 2-(3,5-Dichloropyridin-2-yl)-2,2-difluoroethan-1-ol

HRID 623309Notes

Reaction equation

HRID 623309 reaction equation
[Cl:1][C:2]1[C:3]([C:9]([F:16])([F:15])[C:10](OCC)=[O:11])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[BH4-].[Na+].Cl.O>C(O)C>[Cl:1][C:2]1[C:3]([C:9]([F:15])([F:16])[CH2:10][OH:11])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 4311764Sodium borohydrideHCID 86732541Ethyl (3,5-dichloropyridin-2-yl)(difluoro)acetate

Product 1

HCID 867325422-(3,5-Dichloropyridin-2-yl)-2,2-difluoroethan-1-ol

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 10 g (37 mmol) of ethyl (3,5-dichloropyridin-2-yl)(difluoro)acetate (Int-7) in 60 mL of ethanol, were added portionwise at 0° C., 1.05 g (27.7 mmol) of sodium borohydride. The reaction mixture was stirred below 10° C. for 2 hours. 30 mL of 1 N HCl were then slowly added followed by 500 mL of water. The aequeous phase was extracted three times by 300 mL of ethyl acetate and the organic phase was successively washed with brine, water and dried over magnesium sulfate. After evaporation of the solvent under vacuum 8.5 g of yellow oil were obtained. After trituration in diisopropyl ether and filtration 6.8 g (80%) of 2-(3,5-dichloropyridin-2-yl)-2,2-difluoroethanol (Int-9) were obtained as a white solid. Mp (melting point)=56° C. (M+1)=228. 19F-NMR (235 MHz, CDCl3) δ (ppm): −105.85 (CF2).

Workup

  1. extractionThe aequeous phase was extracted three times by 300 mL of ethyl acetate
  2. washthe organic phase was successively washed with brine, water
  3. dry with materialdried over magnesium sulfate
  4. customAfter evaporation of the solvent under vacuum 8.5 g of yellow oil
  5. customwere obtained
  6. filtrationAfter trituration in diisopropyl ether and filtration 6.8 g (80%) of 2-(3,5-dichloropyridin-2-yl)-2,2-difluoroethanol (Int-9)
  7. customwere obtained as a white solid
  8. customMp (melting point)=56° C. (M+1)=228

Sources & evidence

ORD record
ord-f5a02f319c614510b25985e63fc3ec89
Source dataset
uspto-grants-2016_04
Patent number
US09301526B2

Reaction notes

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