Sodium hydride → tert-Butyl (3S,5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-oxirane-2-ylpiperidine-1-carboxylate

HRID 1184114Notes

Reaction equation

HRID 1184114 reaction equation
[I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH:9]([C@@H:11]1[CH2:16][C@H:15]([N:17]([C:22]([C:24]2[N:28]([CH2:29][CH2:30][CH2:31][CH2:32][O:33][CH3:34])[C:27]3[CH:35]=[CH:36][CH:37]=[CH:38][C:26]=3[N:25]=2)=[O:23])[CH2:18][CH:19]([CH3:21])[CH3:20])[CH2:14][N:13]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:12]1)=[O:10].[Cl-].[NH4+]>CS(C)=O>[CH3:34][O:33][CH2:32][CH2:31][CH2:30][CH2:29][N:28]1[C:27]2[CH:35]=[CH:36][CH:37]=[CH:38][C:26]=2[N:25]=[C:24]1[C:22]([N:17]([CH2:18][CH:19]([CH3:20])[CH3:21])[C@H:15]1[CH2:16][C@@H:11]([CH:9]2[CH2:2][O:10]2)[CH2:12][N:13]([C:39]([O:41][C:42]([CH3:43])([CH3:45])[CH3:44])=[O:40])[CH2:14]1)=[O:23]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 58355644tert-butyl (3R,5S)-3-formyl-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1-carboxylate

Product 1

HCID 58355125tert-Butyl (3S,5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-oxirane-2-ylpiperidine-1-carboxylateYield 49.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Trimethylsulfoxonium iodide (240 mg) was dissolved in DMSO (5 ml), sodium hydride (60% in oil, 45 mg) was added, and the mixture was stirred at room temperature for 30 min. A solution of tert-butyl (3R,5S)-3-formyl-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1-carboxylate (450 mg) in DMSO (10 ml) was added and the mixture was stirred at room temperature for 30 min. The reaction mixture was poured into saturated aqueous ammonium chloride solution and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give the object product (230 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 30 min
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe extract was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. washa fraction eluted with ethyl acetate
  6. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-e81799e46e27425d9f90b8cd936447df
Source dataset
uspto-grants-2014_03
Patent number
US08664380B2

Reaction notes

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