Tetrahydrofuran → (2R*,3R*,4R*,6R*)-2-Diphenylmethyl-3-(2-methoxybenzylamino)-6-phenethyl-1-azabicyclo[2.2.2]octane

HRID 862111Notes

Reaction equation

HRID 862111 reaction equation
[C:1]1([CH:7]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:8]2[C:13](=O)[C@@H:12]3[CH2:15][CH2:16][N:9]2[C@H:10]([CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:11]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:31][O:32][C:33]1[CH:40]=[CH:39][CH:38]=[CH:37][C:34]=1[CH2:35][NH2:36].C1COCC1.B1C2CCCC1CCC2>C1(C)C=CC=CC=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>[C:25]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C@@H:8]2[C@H:13]([NH:36][CH2:35][C:34]3[CH:37]=[CH:38][CH:39]=[CH:40][C:33]=3[O:32][CH3:31])[C@@H:12]3[CH2:15][CH2:16][N:9]2[C@H:10]([CH2:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:11]3)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 789669-Borabicyclo(3.3.1)nonaneHCID 812922-MethoxybenzylamineHCID 54156123(2R*,4R*,6R*)-2-Diphenylmethyl-6-phenethylquinuclidin-3-one

Product 1

HCID 70115251(2R*,3R*,4R*,6R*)-2-Diphenylmethyl-3-(2-methoxybenzylamino)-6-phenethyl-1-azabicyclo[2.2.2]octaneYield 23.3%

Reagents, catalysts & solvents 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-CatalystHCID 1140TolueneSolvent

Procedure

Compound 7 (357 mg, 0.904 mmol), 2-methoxybenzylamine (189 mg, 1.38 mmol) and camphorsulfonic acid (2.0 mg) were dissolved in toluene (30 ml), and the resultant mixture was heated at reflux for 3 days under a dehydrating condition with MS 4A. After replacement of the solvent with THF a solution of 9-BBN (0.5M in THF, 5.4 ml) was added, and the resultant mixture was stirred for 4 days at room temperature. After evaporation of the solvent the residue was basified at pH=13, extracted with CH2Cl2, dried over Na2SO4, and concentrated down. The crude material was purified by combination of column chromatography (silica-gel, MeOH/CH2Cl2), preparative TLC (silica-gel, 10% MeOH/CH2 Cl2) and crystallization from MeOH to provide pure compound 8 (109 mg, 23%).

Workup

  1. customAfter evaporation of the solvent the residue
  2. extractionextracted with CH2Cl2
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated down
  5. customThe crude material was purified by combination of column chromatography (silica-gel, MeOH/CH2Cl2), preparative TLC (silica-gel, 10% MeOH/CH2 Cl2) and crystallization from MeOH

Sources & evidence

ORD record
ord-1a9900c299204e34bea8d0b7814da216
Source dataset
uspto-grants-1998_02
Patent number
US05716965

Reaction notes

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