Cesium carbonate → HCID 58355516, compound

HRID 1260000Notes

Reaction equation

HRID 1260000 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([N:12]([CH2:34][CH:35]([CH3:37])[CH3:36])[C@H:13]1[CH2:18][C@@H:17]([C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:20])[CH2:16][N:15]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:14]1)=[O:11].Br[CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C.O>[CH2:44]([O:43][C:41](=[O:42])[CH2:40][CH2:39][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([N:12]([CH2:34][CH:35]([CH3:37])[CH3:36])[C@H:13]1[CH2:18][C@@H:17]([C:19]([N:21]2[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)=[O:20])[CH2:16][N:15]([C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])[CH2:14]1)=[O:11])[CH3:45]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 68320Ethyl 3-bromopropionate2×HCID 58355717tert-Butyl (3S,5R)-3-{(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino)-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

Product 1

HCID 58355516HCID 58355516, compoundYield 73.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl (3S,5R)-3-[(1H-benzimidazol-2-ylcarbonyl) (2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (257 mg) and ethyl 3-bromopropanoate (181 mg) in N,N-dimethylacetamide (5 ml) was added cesium carbonate (489 mg), and the mixture was stirred at 70° C. for 15 hr. Ethyl 3-bromopropanoate (181 mg) was added to the reaction mixture, and the mixture was further stirred at 70° C. for 5 hr. The reaction mixture was cooled to room temperature, diluted with water, 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 (6:4) was concentrated under reduced pressure to give the object product (225 mg).

Workup

  1. stirringthe mixture was further stirred at 70° C. for 5 hr
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. washa fraction eluted with ethyl acetate-hexane (6:4)
  8. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-f6eb0ef2b34c4769a9cd22085cba0d93
Source dataset
uspto-grants-2013_06
Patent number
US08466282B2

Reaction notes

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