Water → tert-butyl (3S,5R)-3-{[(5,6-difluoro-1H-benzimidazol-2-yl)carbonyl](2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 2168916Notes

Reaction equation

HRID 2168916 reaction equation
[F:1][C:2]1[C:14]([F:15])=[CH:13][C:5]2[NH:6][C:7]([C:9](Cl)(Cl)Cl)=[N:8][C:4]=2[CH:3]=1.[CH3:16][CH:17]([CH3:41])[CH2:18][NH:19][C@H:20]1[CH2:25][C@@H:24]([C:26]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:27])[CH2:23][N:22]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:21]1.C(=O)([O-])[OH:43].[Na+].O>C1COCC1>[F:1][C:2]1[C:14]([F:15])=[CH:13][C:5]2[NH:6][C:7]([C:9]([N:19]([CH2:18][CH:17]([CH3:41])[CH3:16])[C@H:20]3[CH2:25][C@@H:24]([C:26]([N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[O:27])[CH2:23][N:22]([C:34]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:35])[CH2:21]3)=[O:43])=[N:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 231319195,6-difluoro-2-(trichloromethyl)-1H-benzimidazoleHCID 59356577tert-Butyl (3S,5R)-3-(isobutylamino)-5-(morpholine-4-carbonyl)piperidine-1-carboxylate

Product 1

HCID 58355165tert-butyl (3S,5R)-3-{[(5,6-difluoro-1H-benzimidazol-2-yl)carbonyl](2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylateYield 70.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5,6-difluoro-2-(trichloromethyl)-1H-benzimidazole (500 mg) and tert-butyl (3S,5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (680 mg) in THF (50 ml) were added sodium hydrogen carbonate (1.3 g) and water (20 ml), and the mixture was stirred at room temperature for 1 hr and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:1-1:0) was concentrated under reduced pressure to give the object product (710 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. washa fraction eluted with ethyl acetate-hexane (1:1-1:0)
  6. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-a26fdc1d8a2e43cd97d35b9585626768
Source dataset
uspto-grants-2015_06
Patent number
US09045436B2

Reaction notes

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