Water → HCID 58355471, compound

HRID 2168915Notes

Reaction equation

HRID 2168915 reaction equation
Cl[C:2](Cl)(Cl)[C:3]1[NH:7][C:6]2[CH:8]=[CH:9][CH:10]=[CH:11][C:5]=2[N:4]=1.[CH3:14][CH:15]([CH3:35])[CH2:16][NH:17][C@@H:18]1[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:21][C@H:20]([C:31]([O:33][CH3:34])=[O:32])[CH2:19]1.C(=O)([O-])[OH:37].[Na+].O>C1COCC1>[NH:4]1[C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=[C:3]1[C:2]([N:17]([CH2:16][CH:15]([CH3:35])[CH3:14])[C@@H:18]1[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])[CH2:21][C@H:20]([C:31]([O:33][CH3:34])=[O:32])[CH2:19]1)=[O:37]

Participants

6

Reactant 4

HCID 962WaterHCID 77133Benzimidazole, 2-trichloromethyl-HCID 516892Sodium BicarbonateHCID 593566071-tert-butyl 3-methyl (3R,5S)-5-[(2-methylpropyl)amino]piperidine-1,3-dicarboxylate

Product 1

HCID 58355471HCID 58355471, compoundYield 83.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

2-(Trichloromethyl)-1H-benzimidazole (19 g) and 1-tert-butyl 3-methyl(3R,5S)-5-[(2-methylpropyl)amino]piperidine-1,3-dicarboxylate (25 g) were dissolved in THF (1200 ml), sodium hydrogen carbonate (67 g) and water (600 ml) were added, and the mixture was stirred at room temperature for 1 hr and at 50° C. for 1 hr. After evaporation of the solvent, the residue was extracted 3 times with ethyl acetate (700 ml). The extract was washed successively with 10%-aqueous citric acid solution (500 ml) and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (1000 ml), subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give the object product (30.6 g).

Workup

  1. customAfter evaporation of the solvent
  2. extractionthe residue was extracted 3 times with ethyl acetate (700 ml)
  3. washThe extract was washed successively with 10%-aqueous citric acid solution (500 ml) and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionThe residue was dissolved in ethyl acetate (1000 ml)
  7. washa fraction eluted with ethyl acetate
  8. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-9c5cc270f85b47debae8dee4bc44ad1a
Source dataset
uspto-grants-2015_06
Patent number
US09045436B2

Reaction notes

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