Ammonium Acetate → tert-Butyl 4-(1-aminoethyl)piperidine-1-carboxylate

HRID 1853467Notes

Reaction equation

HRID 1853467 reaction equation
[C:1]([CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)(=O)[CH3:2].C([O-])(=O)C.[NH4+].C([BH3-])#[N:23].[Na+]>CO.[OH-].[Na+]>[NH2:23][CH:1]([CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)[CH3:2]

Participants

6

Reactant 3

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 109879834-Acetyl-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 22647295tert-Butyl 4-(1-aminoethyl)piperidine-1-carboxylateYield 90%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of tert-butyl 4-acetylpiperidine-1-carboxylate (145 g, 0.64 mol) and ammonium acetate (225 g, 2.9 mol) in methanol (2 L) was stirred at room temperature for 1.5 hours. Sodium cyanoborohydride (30 g, 0.48 mol) was added in one portion and the stirring was continued overnight at room temperature. The reaction mixture was poured in 2N aq. NaOH (2 L) and extracted with dichloromethane (2×1 L). The combined extracts were washed with water (1 L), brine (0.3 L), and evaporated to dryness. The residue was dissolved in TBME (1.5 L), dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The residue was purified by bulb to bulb distillation at 180° C. and 0.1 mbar to afford the title compound as a colorless oil that partly solidified upon standing (131 g, 90% yield).

Workup

  1. waitthe stirring was continued overnight at room temperature
  2. extractionextracted with dichloromethane (2×1 L)
  3. washThe combined extracts were washed with water (1 L), brine (0.3 L)
  4. customevaporated to dryness
  5. dissolutionThe residue was dissolved in TBME (1.5 L)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness under reduced pressure
  9. distillationThe residue was purified by bulb to bulb distillation at 180° C.

Sources & evidence

ORD record
ord-5ca905bdd1a94d45afa5a5e0c28a2c1a
Source dataset
uspto-grants-2015_02
Patent number
US08962642B2

Reaction notes

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