Hydrochloric Acid → 4-{1-(3,4-Dimethoxyphenoxy)-4-[8-(methylamino)-3-azabicyclo-[3.2.1]oct-3-yl]butyl}benzonitrile

HRID 411531Notes

Reaction equation

HRID 411531 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]([O:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[C:33]([O:39][CH3:40])[CH:32]=2)[CH2:10][CH2:11][CH2:12][N:13]2[CH2:19][CH:18]3[CH:20]([N:21](C)[C:22](=O)[O:23]C(C)(C)C)[CH:15]([CH2:16][CH2:17]3)[CH2:14]2)=[CH:5][CH:4]=1)#[N:2].Cl>C(OCC)(=O)C>[OH-:23].[NH4+:2].[CH3:40][O:39][C:33]1[CH:32]=[C:31]([CH:36]=[CH:35][C:34]=1[O:37][CH3:38])[O:30][CH:9]([C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=1)[CH2:10][CH2:11][CH2:12][N:13]1[CH2:19][CH:18]2[CH:20]([NH:21][CH3:22])[CH:15]([CH2:16][CH2:17]2)[CH2:14]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 18540880Tert-butyl 3-[4-(4-cyanophenyl)-4-(3,4-dimethoxyphenoxy)butyl]-3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate

Product 2

HCID 14923Ammonium HydroxideHCID 185409394-{1-(3,4-Dimethoxyphenoxy)-4-[8-(methylamino)-3-azabicyclo-[3.2.1]oct-3-yl]butyl}benzonitrileYield 120.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A suspension of tert-butyl 3-[4-(4-cyanophenyl)-4-(3,4-dimethoxyphenoxy)butyl]-3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate (see step (iv) above; 2.67 g, 4.86 mmol) in ethyl acetate saturated with HCl (60 mL) was stirred overnight at 25° C. under nitrogen. The mixture was partitioned with water (100 mL) and ethyl acetate (50 mL). The aqueous layer was washed with ethyl acetate (50 mL) before being separated, basified with saturated sodium bicarbonate (50 mL) and then extracted with dichloromethane (3×50 mL). The organic extracts were dried (Na2SO4), filtered, concentrated in vacuo and then chromatographed on silica gel, eluting with dichloromethane:methanol:concentrated ammonium hydroxide (92:7:1), to afford 1.32 g (61%) of the title compound as a yellow oil.

Workup

  1. customThe mixture was partitioned with water (100 mL) and ethyl acetate (50 mL)
  2. washThe aqueous layer was washed with ethyl acetate (50 mL)
  3. custombefore being separated
  4. extractionextracted with dichloromethane (3×50 mL)
  5. dry with materialThe organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customchromatographed on silica gel
  9. washeluting with dichloromethane

Sources & evidence

ORD record
ord-fd5eaa59aa07495792cae7183a5d8028
Source dataset
uspto-grants-2003_05
Patent number
US06559162B2

Reaction notes

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