Hydrochloric Acid → (1R*,2R*,5R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-8-methyl-1-phenyl-8-azabicyclo[3.2.1]octane hydrochloride

HRID 2088160Notes

Reaction equation

HRID 2088160 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH2:13][O:14][C@@H:15]2[CH2:21][CH2:20][C@@H:19]3[NH:22][C@@:16]2([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:17][CH2:18]3)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[C:31](=O)([O-])[O-].[K+].[K+].CI.[ClH:39]>CN(C)C=O.C(OCC)C.O>[ClH:39].[F:11][C:9]([F:12])([F:10])[C:7]1[CH:6]=[C:5]([CH2:13][O:14][C@@H:15]2[CH2:21][CH2:20][C@@H:19]3[N:22]([CH3:31])[C@@:16]2([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:17][CH2:18]3)[CH:4]=[C:3]([C:2]([F:29])([F:1])[F:30])[CH:8]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 86586647(1R*,2R*,5R*)-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane

Product 1

HCID 86586692(1R*,2R*,5R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-8-methyl-1-phenyl-8-azabicyclo[3.2.1]octane hydrochloride

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolvent

Procedure

(1R*,2R*,5R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane (Example 60; 117 mg, 0.27 mmol) was dissolved in dimethylformamide (2 ml) and potassium carbonate (149 mg, 1.08 mmol) and methyl iodide (0.02 ml, 0.32 mmol) added and the mixture stirred at room temperature for 1 hour. The reaction mixture was poured into water then extracted with ethyl acetate (×2), dried (MgSO4), and concentrated in vacuo to give a yellow oil. This was purified by flash column chromatography [7.5%-10% methanol in dichloromethane] to give a yellow oil. The oil was dissolved in diethyl ether (2 ml) and 1 equivalent of1N hydrogen chloride in diethyl ether added to give the title compound as a yellow solid which was filtered and dried at 60° C. in vacuo.

Workup

  1. extractionthen extracted with ethyl acetate (×2)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give a yellow oil
  5. customThis was purified by flash column chromatography [7.5%-10% methanol in dichloromethane]
  6. customto give a yellow oil

Sources & evidence

ORD record
ord-e39c79743b6d43518d12266c1b9e0456
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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