Hydrochloric Acid → 4-[2-Hydroxy-3-[8-(methylamino)-3-azabicyclo[3.2.1]oct-3-yl]-propoxy}benzonitrile
Reaction equation
[C:1]([C:3]1[CH:30]=[CH:29][C:6]([O:7][CH2:8][CH:9]([OH:28])[CH2:10][N:11]2[CH2:17][CH:16]3[CH:18]([N:19](C)[C:20](=O)OC(C)(C)C)[CH:13]([CH2:14][CH2:15]3)[CH2:12]2)=[CH:5][CH:4]=1)#[N:2].Cl>C(OCC)(=O)C>[OH-:7].[NH4+:2].[OH:28][CH:9]([CH2:10][N:11]1[CH2:12][CH:13]2[CH:18]([NH:19][CH3:20])[CH:16]([CH2:15][CH2:14]2)[CH2:17]1)[CH2:8][O:7][C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:30][CH:29]=1Participants
Reactant 2
Product 2
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 25 °C
Procedure
A suspension of tert-butyl 3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate (see step (i) above; 3.15 g, 7.58 mmol) in ethyl acetate saturated with HCl (40 mL) was stirred for 5 h at 25° C. under nitrogen. The mixture was partitioned with water (100 mL) and ethyl acetate (50 mL). The aqueous layer was separated and washed with ethyl acetate. The aqueous layer was separated, basified with saturated sodium bicarbonate (30 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 (88:10:2), to afford 2.30 g (96%) of the title compound as a colorless oil.
Workup
- customThe mixture was partitioned with water (100 mL) and ethyl acetate (50 mL)
- customThe aqueous layer was separated
- washwashed with ethyl acetate
- customThe aqueous layer was separated
- extractionextracted with dichloromethane (3×50 mL)
- dry with materialThe organic extracts were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customchromatographed on silica gel
- washeluting with dichloromethane
Sources & evidence
- ORD record
- ord-1c50fa3ccae14ad08327660253e16939
- Source dataset
- uspto-grants-2003_05
- Patent number
- US06559162B2
Reaction notes
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