Sodium Hydroxide → rac-(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-thiophen-2-yl-bicyclo[2.2.2]oct-5-en-2-ol

HRID 220298Notes

Reaction equation

HRID 220298 reaction equation
COCCO[AlH2-]OCCOC.[Na+].[NH:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[N:15]=[C:14]1[CH2:22][CH2:23][CH2:24][N:25]([CH3:43])[C:26](=O)[CH2:27][C:28]1([OH:41])[CH2:33][CH:32]2[CH2:34][CH2:35][CH:29]1[CH:30]=[C:31]2[C:36]1[S:37][CH:38]=[CH:39][CH:40]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[NH:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[N:15]=[C:14]1[CH2:22][CH2:23][CH2:24][N:25]([CH3:43])[CH2:26][CH2:27][C:28]1([OH:41])[CH2:33][CH:32]2[CH2:34][CH2:35][CH:29]1[CH:30]=[C:31]2[C:36]1[S:37][CH:38]=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 16684438Red-AlHCID 68412936rac-(1R*,2R*,4R*)-N-[3-(1H-benzoimidazol-2-yl)-propyl]-2-(2-hydroxy-5-thiophen-2-yl-bicyclo[2.2.2]oct-5-en-2-yl)-N-methyl-acetamide

Product 1

HCID 68415030rac-(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-thiophen-2-yl-bicyclo[2.2.2]oct-5-en-2-olYield 79.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

0.196 mL of a Red-Al solution (65% in toluene) was added dropwise at 0° C. to a solution of 70 mg of rac-(1R*,2R*,4R*)-N-[3-(1H-benzoimidazol-2-yl)-propyl]-2-(2-hydroxy-5-thiophen-2-yl-bicyclo[2.2.2]oct-5-en-2-yl)-N-methyl-acetamide in toluene (0.8 mL). The reaction mixture was stirred for 30 min at 0° C. then the temperature was allowed to increase to rt for 3.5 h. The mixture was carefully poured onto a mixture of 1M-NaOH (6.1 mL) and ice. The mixture was stirred for 5 min until rt and extracted with toluene. The aq. phase was extracted with toluene. The combined toluene phase was washed with 1M-NaOH and brine, dried over anh. Na2SO4 and concentrated in vacuo to yield 54 mg of rac-(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-thiophen-2-yl-bicyclo[2.2.2]oct-5-en-2-ol as a colorless solid.

Workup

  1. temperatureto increase to rt for 3.5 h
  2. stirringThe mixture was stirred for 5 min until rt
  3. extractionextracted with toluene
  4. extractionThe aq. phase was extracted with toluene
  5. washThe combined toluene phase was washed with 1M-NaOH and brine
  6. dry with materialdried over anh. Na2SO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5be5f56fe5ce4232ba831ba629018b01
Source dataset
uspto-grants-2012_06
Patent number
US08202885B2

Reaction notes

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