Potassium Carbonate → Tert-butyl 3-[4-(4-cyanophenyl)-4-(3,4-dimethoxyphenoxy)butyl]-3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate

HRID 411530Notes

Reaction equation

HRID 411530 reaction equation
[CH:1]12[CH:8]([N:9]([CH3:17])[C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:5]([CH2:6][CH2:7]1)[CH2:4][NH:3][CH2:2]2.CS(O[CH2:23][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(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:44]([C:41]1[CH:40]=[CH:39][C:38]([CH:26]([O:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH3:37])[CH:29]=2)[CH2:25][CH2:24][CH2:23][N:3]2[CH2:4][CH:5]3[CH:8]([N:9]([CH3:17])[C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:14])[CH3:15])[CH:1]([CH2:7][CH2:6]3)[CH2:2]2)=[CH:43][CH:42]=1)#[N:45]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 18541001Tert-butyl 3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamateHCID 218675684-(4-Cyanophenyl)-4-(3,4-dimethoxyphenoxy)butyl methanesulfonate

Product 1

HCID 18540880Tert-butyl 3-[4-(4-cyanophenyl)-4-(3,4-dimethoxyphenoxy)butyl]-3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamateYield 60.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of tert-butyl 3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate (Preparation D; 2.60 g, 10.9 mmol), 4-(4-cyanophenyl)-4-(3,4-dimethoxyphenoxy)butyl methanesulfonate (see step (iii) above; 4.40 g, 10.9 mmol), and potassium carbonate (1.50 g, 10.9 mmol) in DMF (50 mL) was heated at 90° C. under nitrogen for 4 h. The mixture was partitioned with water (50 mL) and diethyl ether (50 mL). The aqueous layer was extracted with diethyl ether (2×50 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 3.60 g (60%) of the sub-title compound as an amorphous solid.

Workup

  1. customThe mixture was partitioned with water (50 mL) and diethyl ether (50 mL)
  2. extractionThe aqueous layer was extracted with diethyl ether (2×50 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-c95062bd67c04494a8d36f07695feaa9
Source dataset
uspto-grants-2003_05
Patent number
US06559162B2

Reaction notes

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