Sodium cyanoborohydride → rac-N-(3-{[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-methyl-amino}-propyl)-3-methoxy-2-methoxymethyl-2-methyl-propionamide

HRID 220312

Reaction equation

HRID 220312 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][C:5]1([OH:19])[CH2:10][CH:9]2[CH2:11][CH2:12][CH:6]1[CH:7]=[C:8]2[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:20][O:21][CH2:22][C:23]([CH2:32][O:33][CH3:34])([CH3:31])[C:24]([NH:26][CH2:27][CH2:28][CH:29]=O)=[O:25].C([BH3-])#N.[Na+]>C(Cl)Cl.CC(O)=O>[OH:19][C@@:5]1([CH2:4][CH2:3][N:2]([CH3:1])[CH2:29][CH2:28][CH2:27][NH:26][C:24](=[O:25])[C:23]([CH2:32][O:33][CH3:34])([CH3:31])[CH2:22][O:21][CH3:20])[CH2:10][C@H:9]2[CH2:11][CH2:12][C@@H:6]1[CH:7]=[C:8]2[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 68415512rac-(1R*,2R*,4R*)-2-(2-methylamino-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-olHCID 866419283-methoxy-2-methoxymethyl-2-methyl-N-(3-oxo-propyl)-propionamide

Product 1

HCID 68412527rac-N-(3-{[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-methyl-amino}-propyl)-3-methoxy-2-methoxymethyl-2-methyl-propionamideYield 55%

Reagents, catalysts & solvents 1

HCID 21922555Acetic acid methylene chlorideSolvent

Procedure

50 mg of rac-(1R*,2R*,4R*)-2-(2-methylamino-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol were dissolved in DCM/AcOH. 46 mg of 3-methoxy-2-methoxymethyl-2-methyl-N-(3-oxo-propyl)-propionamide and 50 mg of sodium cyanoborohydride were added. The reaction mixture was stirred for 3 days at room temperature, quenched with sat.-NaHCO3 and extracted with DCM. The organic phase was washed with brine, dried over anh. Na2SO4 and concentrated in vacuo. The resulting crude material was purified by CC using EtOAc/MeOH/NEt3 90/10/1 as eluant to yield 49 mg of rac-N-(3-{[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-methyl-amino}-propyl)-3-methoxy-2-methoxymethyl-2-methyl-propionamide as a yellow oil.

Workup

  1. customquenched with sat.-NaHCO3
  2. extractionextracted with DCM
  3. washThe organic phase was washed with brine
  4. dry with materialdried over anh. Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting crude material was purified by CC

Sources & evidence

ORD record
ord-6600ab8a041d4cfea4533044a995ee87
Source dataset
uspto-grants-2012_06
Patent number
US08202885B2

Linked notes

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