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

HRID 2266222Notes

Reaction equation

HRID 2266222 reaction equation
[Cl:1][C:2]1[C:3]([F:29])=[C:4]([CH:8]([O:22][CH2:23][C:24](OCC)=[O:25])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+]>CO>[Cl:1][C:2]1[C:3]([F:29])=[C:4]([CH:8]([O:22][CH2:23][CH2:24][OH:25])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 59382873(R)-tert-butyl 3-((3-chloro-2-fluorophenyl)(2-ethoxy-2-oxoethoxy)methyl)piperidine-1-carboxylate

Product 1

HCID 59382915(R)-tert-butyl 3-((3-chloro-2-fluorophenyl)(2-hydroxyethoxy)methyl)piperidine-1-carboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (R)-tert-butyl 3-((3-chloro-2-fluorophenyl)(2-ethoxy-2-oxoethoxy)-methyl)piperidine-1-carboxylate (4.368 g, 10.2 mmol) in MeOH (85 mL) was added NaBH4 (3.18 g, 81.5 mmol) in portions such that the temperature remained below 40° C. After addition, the mixture was stirred at rt for 2˜3 h. TLC showed the starting material had disappeared. The solvent was removed in vaczio 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)(2-hydroxyethoxy)methyl)piperidine-1-carboxylate (3.5 g, 89%). 1H NMR (400 MHz, CDCl3): 1.18 (m, 1H), 1.38-1.46 (s, 9H), 1.65 (m, 1H), 1.85 (m, 2H), 2.66 (m, 1H), 3.25 (m, 1H), 3.38 (m, 2H), 3.69 (m, 3H), 3.93 (m, 1H), 4.52 (m, 6H); MS (E/Z): 388 (M+1)

Workup

  1. customremained below 40° C
  2. additionAfter addition
  3. customThe solvent was removed in vaczio
  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-92eadf7a9da24e40a475bb1277de645d
Source dataset
uspto-grants-2010_12
Patent number
US07858624B2

Reaction notes

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