Ammonium Acetate → 1-[(4-Methylphenyl)methyl]piperidin-4-amine

HRID 49444

Reaction equation

HRID 49444 reaction equation
[CH3:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:22].[Na+]>CO>[CH3:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][CH:10]([NH2:22])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 119595411-(4-Methylbenzyl)piperidin-4-one

Product 1

HCID 126418361-[(4-Methylphenyl)methyl]piperidin-4-amineYield 48.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 4.25 g (21 mmol) of 1-(4-methylbenzyl)-4-piperidinone 124 in 200 mL of anhydrous methanol was added 32.2 g (420 mmol) of ammonium acetate and 25 g of 3A molecular sieves. After stirring 30 min, 5.25 g (84 mmol) of sodium cyanoborohydride was added portionwise. After stirring 16 hours, the mixture was gravity filtered and the methanol evaporated under vacuum. The residue was partitioned between ether and ice/HCl. The acidic aqueous layer was extracted twice with ether, made basic with 50% aqueous NaOH and ice, and extracted with CH2Cl2 to give 2.1 g (48%) of the title amine 125 as a thick oil. GC/MS showed a molecular ion of 204. The product was used as is without further purification.

Workup

  1. stirringAfter stirring 16 hours
  2. filtrationfiltered
  3. customthe methanol evaporated under vacuum
  4. customThe residue was partitioned between ether and ice/HCl
  5. extractionThe acidic aqueous layer was extracted twice with ether
  6. extractionextracted with CH2Cl2

Sources & evidence

ORD record
ord-9bf5a068f7d446908f3027c600854fa9
Source dataset
uspto-grants-2004_03
Patent number
US06706740B2

Linked notes

Loading…