Sodium borohydride → (R)-tert-butyl 3-((3-chloro-2-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate

HRID 1254293Notes

Reaction equation

HRID 1254293 reaction equation
[Cl:1][C:2]1[C:3]([F:23])=[C:4]([CH:20]=[CH:21][CH:22]=1)[C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]1)=[O:6].[BH4-].[Na+]>CO>[Cl:1][C:2]1[C:3]([F:23])=[C:4]([CH:5]([OH:6])[C@@H:7]2[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:8]2)[CH:20]=[CH:21][CH:22]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 59382847(R)-tert-butyl 3-(3-chloro-2-fluorobenzoyl)piperidine-1-carboxylate

Product 1

HCID 59383063(R)-tert-butyl 3-((3-chloro-2-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylateYield 56%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (R)-tert-butyl 3-(3-chloro-2-fluorobenzoyl)piperidine-1-carboxylate (7.75 g, 22.7 mmol) in MeOH (160 mL) was added NaBH4 (6.9 g, 182 mmol) in portions such that the temperature remained below 40° C. After addition, the mixture was stirred at rt for 3 h. TLC showed the start material had disappeared. The solvent was removed in vacuo and the residue was partitioned between water and EtOAc. The organic layer was washed with H2O and brine, dried over Na2SO4 and evaporated to give (R)-tert-butyl 3-((3-chloro-2-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (4.35 g, 56%) which was used in the next step without purification. MS (E/Z): 344 (M+H+).

Workup

  1. customremained below 40° C
  2. additionAfter addition
  3. customThe solvent was removed in vacuo
  4. customthe residue was partitioned between water and EtOAc
  5. washThe organic layer was washed with H2O and brine
  6. dry with materialdried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-a8310941c4a140f4ae5291c106d18ebb
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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