Diethylamine → 4-[1-Benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-N,N-diethyl-benzamide

HRID 2085456Notes

Reaction equation

HRID 2085456 reaction equation
[CH2:1]([NH:3][CH2:4][CH3:5])[CH3:2].C[Al](C)C.C[O:11][C:12](=O)[C:13]1[CH:18]=[CH:17][C:16]([C:19]2([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=3)[CH2:24][CH2:23][N:22]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:21][CH2:20]2)=[CH:15][CH:14]=1.C([O-])(O)=O.[Na+]>>[CH2:25]([N:22]1[CH2:23][CH2:24][C:19]([C:16]2[CH:17]=[CH:18][C:13]([C:12]([N:3]([CH2:4][CH3:5])[CH2:1][CH3:2])=[O:11])=[CH:14][CH:15]=2)([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=2)[CH2:20][CH2:21]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 4

HCID 8021DiethylamineHCID 516892Sodium BicarbonateHCID 16682925TrimethylaluminumHCID 538358404-[1-Benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-benzoic acid methyl ester

Product 1

HCID 227299104-[1-Benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-N,N-diethyl-benzamideYield 84.2%

Procedure

To a solution of diethyl amine (1.88 mL, 18.2 mmol) in CH2ClCH2Cl (7 mL) at room temperature was added a trimethylaluminum (9.1 mL, 18.2 mmol, 2M in hexanes) dropwise. The reaction mixture was stirred at room temperature for 1 hour. A solution of of 4-[1-Benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-benzoic acid methyl ester (1.51 g, 3.64 mmol) in (CH2)2Cl2 (6 mL) was added and the reaction mixture was heated to reflux for 14 hours. The solution was then cooled 0° C. and sat. aqueous NaHCO3 (15 mL) was added dropwise. The mixture was filtered through celite. The celite cake was washed with CH2Cl2 (40 mL). The organic layer was separated and the aqueous layer was washed with CH2Cl2 (3×30 mL). The combined organic layers were dried (MgSO4) and concentrated. The crude residue was purified by flash chromatography with EtOAc to afford 1.4 g (84% yield) of 4-[1-Benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-N,N-diethyl-benzamide. 1HNMR (400 MHz, CDCl3) δ 7.28-7.16 (comp, 10H), 6.84-6.80 (comp, 2H), 6.68 (dd, 1H), 3.74 (s, 3H), 3.52-3.48 (comp, 2H), 3.39 (s, 2H), 3.24-3.21 (comp, 2H), 2.47-2.42 (comp, 8H), 1.22-1.20 (comp, 3H), 1.19-1.16 (comp, 3H); MS (M+1) 457.2.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 14 hours
  3. temperatureThe solution was then cooled 0° C.
  4. filtrationThe mixture was filtered through celite
  5. washThe celite cake was washed with CH2Cl2 (40 mL)
  6. customThe organic layer was separated
  7. washthe aqueous layer was washed with CH2Cl2 (3×30 mL)
  8. dry with materialThe combined organic layers were dried (MgSO4)
  9. concentrationconcentrated
  10. customThe crude residue was purified by flash chromatography with EtOAc

Sources & evidence

ORD record
ord-b85d911661264f728b15926ebd9652bc
Source dataset
uspto-grants-2004_04
Patent number
US06720336B2

Reaction notes

Loading…