Benzimidazole, 2-trichloromethyl- → tert-Butyl (3S,5R)-3-{(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino)-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 2168956Notes

Reaction equation

HRID 2168956 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]([CH3:39])[CH2:16][NH:17][C@H:18]1[CH2:23][C@@H:22]([C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[O:25])[CH2:21][N:20]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:19]1.C(=O)([O-])[OH:41].[Na+]>O1CCCC1.O>[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]([CH3:39])[CH3:14])[C@H:18]1[CH2:23][C@@H:22]([C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[O:25])[CH2:21][N:20]([C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[CH2:19]1)=[O:41]

Participants

5

Reactant 3

HCID 77133Benzimidazole, 2-trichloromethyl-HCID 516892Sodium BicarbonateHCID 59356577tert-Butyl (3S,5R)-3-(isobutylamino)-5-(morpholine-4-carbonyl)piperidine-1-carboxylate

Product 1

HCID 58355717tert-Butyl (3S,5R)-3-{(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino)-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylateYield 76.8%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

2-(Trichloromethyl)-1H-benzimidazole (2.00 g) and tert-butyl (3S,5R)-3-{(2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (2.84 g) were dissolved in tetrahydrofuran-water (3:2,150 ml), sodium hydrogen carbonate (6.45 g) was added and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The precipitated white solid was collected by filtration, washed with ethyl acetate-hexane (1:1) and dried to give the object product (3.03 g).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with water
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. filtrationThe precipitated white solid was collected by filtration
  8. washwashed with ethyl acetate-hexane (1:1)
  9. customdried

Sources & evidence

ORD record
ord-da73449470f24d9eae0f4843c09b0800
Source dataset
uspto-grants-2015_06
Patent number
US09045436B2

Reaction notes

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