Acetic Acid → tert-Butyl(1-benzylpiperidin-3-yl)carbamate, (R)-

HRID 919561Notes

Reaction equation

HRID 919561 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.CC(O)=O.[BH3-]C#N.[Na+].[CH:23](=O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C([O-])([O-])=O.[K+].[K+]>CO.O>[CH2:23]([N:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 11430Potassium CarbonateHCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 5003444Sodium cyanoborohydride

Product 1

HCID 25417446tert-Butyl(1-benzylpiperidin-3-yl)carbamate, (R)-Yield 104%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of (R)-tert-butyl piperidin-3-ylcarbamate (500 mg, 2.4 mmol) in MeOH (15 mL), AcOH (0.75 mL, 12.4 mmol) and NaCNBH3 (310 mg, 4.8 mmol) were added sequentially. To this stirred solution was added benzaldehyde (0.25 mL, 2.4 mmol) drop-wise. The reaction mixture was stirred at rt for 60 h before saturated K2CO3(aq) solution was added to neutralize it. The reaction mixture was concentrated in vacuo to give a residue which was dissolved in water and extracted with EtOAc (30 mL×3). The combined EtOAc layer was dried over Na2SO4 and concentrated in vacuo to afford the titled intermediate (725 mg, 48%) that was used in the next step without further purification. LC-MS: m/z [M+1]=291.

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customto give a residue which
  4. extractionextracted with EtOAc (30 mL×3)
  5. dry with materialThe combined EtOAc layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-aa58ee8b1d06457b93040ae73522b324
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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