Nitrogen → 1-Benzyl-3,3-difluoropiperidin-4-ol

HRID 714214Notes

Reaction equation

HRID 714214 reaction equation
N#N.[CH2:3]([N:10]1[CH2:15][CH2:14][C:13](O)([OH:16])[C:12]([F:19])([F:18])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[BH4-].[Na+].C([O-])(O)=O.[Na+]>CO>[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[C:12]([F:19])([F:18])[CH2:11]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 574158661-Benzyl-3,3-difluoropiperidine-4,4-diol

Product 1

HCID 594427361-Benzyl-3,3-difluoropiperidin-4-ol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 1-benzyl-3,3-difluoropiperidine-4,4-diol (WO2008/121687 and WO2005/040120) (2.88 g, 11.85 mmol) in dry MeOH (58 mL) was added NaBH4 (672 mg, 17.76 mmol) portionwise at 0° C. The reaction mixture was stirred at 0° C. for 15 min. Aq. 0.1M NaHCO3 (5 mL) was then added and the mixture further stirred for 5 min, dried (MgSO4), filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept-EA, 2:1→1:1) and the title compound obtained as a beige oil. LC-MS-conditions 08: tR=0.42 min; [M+H]+=228.32.

Workup

  1. stirringthe mixture further stirred for 5 min
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was purified by FC (hept-EA, 2:1→1:1)

Sources & evidence

ORD record
ord-88eb076498324501a26d553ab40de736
Source dataset
uspto-grants-2015_11
Patent number
US09187435B2

Reaction notes

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