Acetic Acid → tert-Butyl 4-(benzylamino)piperidine-1-carboxylate

HRID 591668Notes

Reaction equation

HRID 591668 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[CH2:15]([NH2:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.CC(O)=O.[BH3-]C#N.[Na+]>CO>[CH2:15]([NH:22][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7504BenzylamineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 15380687tert-Butyl 4-(benzylamino)piperidine-1-carboxylateYield 111.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (10.0 g, 50.2 mmol) and benzylamine (2.7 mL, 25.1 mmol) in MeOH (30 mL) was added HOAc (1.9 mL, 32.6 mmol), followed by NaCNBH3 (2.0 g, 32.6 mmol) and the reaction was stirred at room temperature overnight. The resulting mixture was quenched with H2O (5 mL) and concentrated in vacuo. The residue was diluted with 0.1 N HCl and washed with Et2O. The aqueous layer was then basified with 2 N NaOH and extracted with Et2O. The organics were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo, to afford tert-butyl 4-(benzylamino)piperidine-1-carboxylate (8.1 g, 56%).

Workup

  1. customThe resulting mixture was quenched with H2O (5 mL)
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with 0.1 N HCl
  4. washwashed with Et2O
  5. extractionextracted with Et2O
  6. washThe organics were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e3ca128299ad4def862806b5cbf1c1f8
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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