Potassium Carbonate → Tert-butyl 3-[2-(4-cyanophenoxy)ethyl]-3-azabicyclo[3.2.1]oct-8-yl-(methyl)carbamate

HRID 411534Notes

Reaction equation

HRID 411534 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][CH:6]=1.[CH:13]12[CH:20]([N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:17]([CH2:18][CH2:19]1)[CH2:16][NH:15][CH2:14]2.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)Cl>[C:9]([C:8]1[CH:11]=[CH:12][C:5]([O:4][CH2:3][CH2:2][N:15]2[CH2:14][CH:13]3[CH:20]([N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH:17]([CH2:18][CH2:19]3)[CH2:16]2)=[CH:6][CH:7]=1)#[N:10]

Participants

6

Reactant 3

HCID 11430Potassium Carbonate2×HCID 24522124-(2-Bromoethoxy)benzonitrileHCID 18541001Tert-butyl 3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate

Product 1

HCID 18540898Tert-butyl 3-[2-(4-cyanophenoxy)ethyl]-3-azabicyclo[3.2.1]oct-8-yl-(methyl)carbamateYield 76%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-(2-bromoethoxy)benzonitrile (see step (i) above; 0.94 g, 4.2 mmol), tert-butyl 3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate (Preparation D; 0.91 g, 3.8 mmol) and K2CO3 (0.79 g, 5.7 mmol) in 15 mL of dry DMF was stirred at 90° C. overnight before additional K2CO3 (1 g) was added. The mixture was diluted with 300 mL of DCM, and the mixture was washed with water. The organic layer was separated, dried with Na2SO4 and then evaporated. The crude product was purified by flash chromatography on silica gel, eluting with DCM:MeOH (10:1) containing 0.1% TEA, to yield 1.1 g (76%) of the sub-tide compound.

Workup

  1. additionwas added
  2. washthe mixture was washed with water
  3. customThe organic layer was separated
  4. dry with materialdried with Na2SO4
  5. customevaporated
  6. customThe crude product was purified by flash chromatography on silica gel
  7. washeluting with DCM:MeOH (10:1)
  8. additioncontaining 0.1% TEA

Sources & evidence

ORD record
ord-af45229c152d45d1a6f430ab5e88bbd5
Source dataset
uspto-grants-2003_05
Patent number
US06559162B2

Reaction notes

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