Potassium Carbonate → HCID 58355678, compound

HRID 1509469Notes

Reaction equation

HRID 1509469 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]([CH3:47])[CH2:24][NH:25][C@H:26]1[CH2:31][C@@H:30]([C:32]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[O:33])[CH2:29][N:28]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:27]1.C(=O)([O-])[O-:49].[K+].[K+]>C(#N)C.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[C:9]([C:11]([N:25]([CH2:24][CH:23]([CH3:47])[CH3:22])[C@H:26]3[CH2:31][C@@H:30]([C:32]([N:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)=[O:33])[CH2:29][N:28]([C:40]([O:42][C:43]([CH3:45])([CH3:44])[CH3:46])=[O:41])[CH2:27]3)=[O:49])[N:8]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])[C:7]=2[CH:21]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 583557496-methoxy-1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazoleHCID 59356577tert-Butyl (3S,5R)-3-(isobutylamino)-5-(morpholine-4-carbonyl)piperidine-1-carboxylate

Product 1

HCID 58355678HCID 58355678, compoundYield 13.9%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
80 °C

Procedure

6-Methoxy-1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazole (330 mg) was dissolved in acetonitrile-water (2:1, 50 ml), and tert-butyl (3S,5R)-3-{(2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (350 mg) was added. Potassium carbonate (1.3 g) was added, and the mixture was stirred at 80° C. for 5 hr. The reaction mixture was concentrated under reduced pressure, acidified (pH 3) with 6M hydrochloric acid, and the mixture was 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 (3:7)-ethyl acetate was concentrated under reduced pressure. The residue was further 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 (82 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionthe mixture was extracted 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 (3:7)-ethyl acetate
  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-341ced26116440dc8c279a4fa2096fd1
Source dataset
uspto-grants-2015_12
Patent number
US09221836B2

Reaction notes

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