Diisopropylamine → N-(4-n-butoxyphenyl)-N-methyl-2-(1-benzyl-4-hydroxypiperidin-4-yl)acetamide

HRID 49960Notes

Reaction equation

HRID 49960 reaction equation
[CH2:1]([O:5][C:6]1[CH:16]=[CH:15][C:9]([N:10]([CH3:14])[C:11](=[O:13])[CH3:12])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].C([N-]C(C)C)(C)C.[Li+].C(NC(C)C)(C)C.C([Li])CCC.[CH2:37]([N:44]1[CH2:49][CH2:48][C:47](=[O:50])[CH2:46][CH2:45]1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O1CCCC1.O>[CH2:1]([O:5][C:6]1[CH:16]=[CH:15][C:9]([N:10]([CH3:14])[C:11](=[O:13])[CH2:12][C:47]2([OH:50])[CH2:48][CH2:49][N:44]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:45][CH2:46]2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 192201-Benzyl-4-piperidoneHCID 2724682Lithium diisopropylamideHCID 17823826HCID 17823826, compoundHCID 178418339Butyllithium

Product 1

HCID 9931398N-(4-n-butoxyphenyl)-N-methyl-2-(1-benzyl-4-hydroxypiperidin-4-yl)acetamideYield 52.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 4′-n-butoxy-N-methylacetanilide (0.34 g) in anhydrous tetrahydrofuran (1.5 mL) was added to a solution of lithium diisopropylamide prepared from diisopropylamine (0.22 mL) and n-butyl lithium (1.58M hexane solution; 1.07 mL) in an anhydrous tetrahydrofuran (1.6 mL) under cooling with ice-water, and the mixture was stirred for 30 minutes. A solution of 1-benzylpiperidin-4-one (0.32 g) in anhydrous tetrahydrofuran solution (1.5 mL) was added to thereto under cooling with ice-water, followed by additional stirring for 30 minutes. After increasing the temperature to room temperature, water was added to the mixture and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off. The titled compound (0.33 g) was obtained by recrystallization of the residue from hexane.

Workup

  1. stirringby additional stirring for 30 minutes
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off

Sources & evidence

ORD record
ord-756478f821114d2aab54a92d47d79ef3
Source dataset
uspto-grants-2004_03
Patent number
US06710060B2

Reaction notes

Loading…