Sodium hydride → (1R*,2R*,5R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088228Notes

Reaction equation

HRID 2088228 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[C@@H:15]2[CH2:16][CH2:17][C@@:11]1([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C@H:12]([OH:18])[CH2:13][CH2:14]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:25][C:26]([F:40])([F:39])[C:27]1[CH:28]=[C:29]([CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1)[CH2:30]Br.C1OCCOCCOCCOCCOCCOC1>C1COCC1>[CH2:3]([N:10]1[C@@H:15]2[CH2:16][CH2:17][C@@:11]1([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C@H:12]([O:18][CH2:30][C:29]1[CH:32]=[C:33]([C:35]([F:37])([F:38])[F:36])[CH:34]=[C:27]([C:26]([F:25])([F:39])[F:40])[CH:28]=1)[CH2:13][CH2:14]2)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 2855718-Crown-6HCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 69688994(1R*,2R*,5R*)-8-Benzyl-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol

Product 1

HCID 86586691(1R*,2R*,5R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octaneYield 127%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% in oil, 90 mg, 2.25 mmol) was washed twice with THF and treated with a solution of (1R,2R,5R)-8-benzyl-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol (Description 53; 79 mg, 0.25 mmol), 3,5-bis(trifluoromethyl)benzyl bromide (350 mg, 1.14 mmol), 18-crown-6 (110 mg, 0.41 mmol) in THF (5 ml). The reaction mixture was stirred at room temperature for 24 hours, quenched with saturated aqueous NH4Cl and extracted into diethyl ether. The combined organic extracts were washed with water, dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (iso-hexane:diethyl ether) to give the title compound (165 mg).

Workup

  1. customquenched with saturated aqueous NH4Cl
  2. extractionextracted into diethyl ether
  3. washThe combined organic extracts were washed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (iso-hexane:diethyl ether)

Sources & evidence

ORD record
ord-e85da03400064f03adc089ddd9e84a47
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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