Potassium Carbonate → HCID 58355468, compound

HRID 2168954Notes

Reaction equation

HRID 2168954 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[C:9]([C:11](Cl)(Cl)Cl)[N:8]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])[C:7]=2[CH:21]=1.[CH3:22][CH:23]([CH3:43])[CH2:24][NH:25][C@@H:26]1[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29][C@H:28]([C:39]([O:41]C)=[O:40])[CH2:27]1.C(=O)([O-])[O-:45].[K+].[K+]>C(#N)C.O>[C:35]([O:34][C:32]([N:30]1[CH2:31][C@@H:26]([N:25]([C:11]([C:9]2[N:8]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])[C:7]3[CH:21]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=3[N:10]=2)=[O:45])[CH2:24][CH:23]([CH3:43])[CH3:22])[CH2:27][C@@H:28]([C:39]([OH:41])=[O:40])[CH2:29]1)=[O:33])([CH3:38])([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 583557496-methoxy-1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazoleHCID 593566071-tert-butyl 3-methyl (3R,5S)-5-[(2-methylpropyl)amino]piperidine-1,3-dicarboxylate

Product 1

HCID 58355468HCID 58355468, compoundYield 25.3%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

6-Methoxy-1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazole (1.42 g) was dissolved in acetonitrile-water (2:1, 150 ml), 1-tert-butyl 3-methyl(3R,5S)-5-{(2-methylpropyl)amino}piperidine-1,3-dicarboxylate (1.02 g) was added, potassium carbonate (5.5 g) was added and the mixture was stirred at 80° C. for 19 hr. The reaction mixture was concentrated under reduced pressure, acidified (pH3) with 6M hydrochloric acid, and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, and a fraction eluted with ethyl acetate-hexane (5:95)-ethyl acetate-ethyl acetate-methanol (85:15) was concentrated under reduced pressure. The residue was subjected to reversed-phase preparative HPLC, and a fraction eluted with water-acetonitrile (9:1-6:4) was collected, basified (pH 10) with saturated aqueous potassium carbonate solution, and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the object product (460 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionextracted with ethyl acetate
  3. dry with materialThe extract was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. washa fraction eluted with ethyl acetate-hexane (5:95)-ethyl acetate-ethyl acetate-methanol (85:15)
  6. concentrationwas concentrated under reduced pressure
  7. washa fraction eluted with water-acetonitrile (9:1-6:4)
  8. customwas collected
  9. extractionextracted with ethyl acetate
  10. dry with materialThe extract was dried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e6aeb14b5d1c4b21add45ec0a9e47736
Source dataset
uspto-grants-2015_06
Patent number
US09045436B2

Reaction notes

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