Potassium Carbonate → 4-[4-[(3-Benzyl-3-azabicyclo[3.2.1]oct-8-yl)(methyl)amino]-1-(3,4 dimethoxyphenoxy)butyl]benzonitrile

HRID 411532Notes

Reaction equation

HRID 411532 reaction equation
[CH2:1]([N:8]1[CH2:14][CH:13]2[CH:15]([NH:16][CH3:17])[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(OC[CH2:24][CH2:25][CH:26]([C:38]1[CH:43]=[CH:42][C:41]([C:44]#[N:45])=[CH:40][CH:39]=1)[O:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH3:37])[CH:29]=1)(=O)=O.[C:46](=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:1]([N:8]1[CH2:14][CH:13]2[CH:15]([N:16]([CH3:46])[CH2:17][CH2:24][CH2:25][CH:26]([C:38]3[CH:39]=[CH:40][C:41]([C:44]#[N:45])=[CH:42][CH:43]=3)[O:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH3:37])[CH:29]=3)[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 185410303-benzyl-N-methyl-3-azabicyclo[3.2.1]octan-8-amineHCID 218675684-(4-Cyanophenyl)-4-(3,4-dimethoxyphenoxy)butyl methanesulfonate

Product 1

HCID 185408934-[4-[(3-Benzyl-3-azabicyclo[3.2.1]oct-8-yl)(methyl)amino]-1-(3,4 dimethoxyphenoxy)butyl]benzonitrileYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-benzyl-N-methyl-3-azabicyclo[3.2.1]octan-8-amine (Preparation B; 1.3 g, 5.95 mmol), 4-(4-cyanophenyl)-4-(3,4-dimethoxyphenoxy)butyl methanesulfonate (Preparation I(iii); 2.41 g, 5.95 mmol), and potassium carbonate (822 mg, 5.95 mmol) in DMF (25 mL) was heated at 90° C. under nitrogen overnight. The mixture was partitioned with water (50 mL) and diethyl ether (40 mL). The aqueous layer was extracted with diethyl ether (2×40 mL). The combined organic extracts were washed with brine (2×30 mL), dried (Na2SO4), filtered and then concentrated in vacuo. The residue was chromatographed on silica gel, eluting with dichloromethane:methanol (98:2), to afford 860 mg (27%) of the sub-title compound.

Workup

  1. customThe mixture was partitioned with water (50 mL) and diethyl ether (40 mL)
  2. extractionThe aqueous layer was extracted with diethyl ether (2×40 mL)
  3. washThe combined organic extracts were washed with brine (2×30 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed on silica gel
  8. washeluting with dichloromethane:methanol (98:2)

Sources & evidence

ORD record
ord-8b51bb6e69f749b8ac6b556b90c68365
Source dataset
uspto-grants-2003_05
Patent number
US06559162B2

Reaction notes

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