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

HRID 220314

Reaction equation

HRID 220314 reaction equation
COCCO[AlH2-]OCCOC.[Na+].[C:13]1([C:19]2[N:20]=[C:21]([CH2:38][CH2:39][C:40]([N:42]([CH2:44][CH2:45][C@:46]3([OH:60])[CH2:51][C@H:50]4[CH2:52][CH2:53][C@@H:47]3[CH:48]=[C:49]4[C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[CH3:43])=O)[N:22]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:23]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[C:13]1([C:19]2[N:20]=[C:21]([CH2:38][CH2:39][CH2:40][N:42]([CH3:43])[CH2:44][CH2:45][C:46]3([OH:60])[CH2:51][CH:50]4[CH2:52][CH2:53][CH:47]3[CH:48]=[C:49]4[C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=3)[N:22]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:23]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 16684438Red-AlHCID 68414528rac-3-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-N-[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-N-methyl-propionamide

Product 1

HCID 68413097rac-(1R*,2R*,4R*)-2-[2-({3-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-propyl}-methyl-amino)-ethyl]-5-phenyl-bicyclo[2.2.2]oct-5-en-2-olYield 97.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

0.241 mL of a Red-Al solution (65% in toluene) was added dropwise at 0° C. to a solution of 131 mg of rac-3-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-N-[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-N-methyl-propionamide in toluene (0.23 mL). The reaction mixture was stirred for 30 min at 0° C. and for 2 h at room temperature. The mixture was carefully poured onto a mixture of 1M-NaOH (1.75 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 phases were washed with 1M-NaOH and brine, dried over anh. Na2SO4 and concentrated in vacuo. The resulting crude material was purified by CC using EtOAc/MeOH/NEt3 as eluant from 100/0/1 to 95/5/1 to yield 125 mg of rac-(1R*,2R*,4R*)-2-[2-({3-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-propyl}-methyl-amino)-ethyl]-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol as a colorless oil.

Workup

  1. stirringThe mixture was stirred for 5 min until rt
  2. extractionextracted with toluene
  3. extractionThe aq. phase was extracted with toluene
  4. washThe combined toluene phases were washed with 1M-NaOH and brine
  5. dry with materialdried over anh. Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude material was purified by CC

Sources & evidence

ORD record
ord-dd22addc3e2642258734be1b6239bea2
Source dataset
uspto-grants-2012_06
Patent number
US08202885B2

Linked notes

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