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Cesium carbonate → 1-tert-Butyl 3-methyl(3R,5S)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1,3-dicarboxylate

HRID 1509432
Notes
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Reaction equation

HRID 1509432 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]([CH2:30][CH:31]([CH3:33])[CH3:32])[C@@H:13]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16][C@H:15]([C:26]([O:28][CH3:29])=[O:27])[CH2:14]1)=[O:11].CS(O[CH2:39][CH2:40][CH2:41][CH2:42][O:43][CH3:44])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O>[CH3:44][O:43][CH2:42][CH2:41][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]([CH2:30][CH:31]([CH3:33])[CH3:32])[C@@H:13]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:16][C@H:15]([C:26]([O:28][CH3:29])=[O:27])[CH2:14]1)=[O:11]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 116870064-Methoxybutyl methanesulfonateHCID 58355471HCID 58355471, compound

Product 1

HCID 583555501-tert-Butyl 3-methyl(3R,5S)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1,3-dicarboxylateYield 80.5%

Reagents, catalysts & solvents 1

HCID 31374
Dimethylacetamide
Solvent

Conditions

Temperature
70 °C

Procedure

1-tert-Butyl 3-methyl (3R,5S)-5-[(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino]piperidine-1,3-dicarboxylate (30 g) and 4-methoxybutyl methanesulfonate (12.5 g) were dissolved in DMA (600 ml), cesium carbonate (32 g) was added, and the mixture was stirred at 70° C. for 12 hr. The reaction mixture was poured into ice water (1000 ml), and the mixture was extracted twice with ethyl acetate (1000 ml). The extract was washed with 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 (1:4-1:1) was concentrated under reduced pressure to give the object product (28.7 g).

Workup

  1. extractionthe mixture was extracted twice with ethyl acetate (1000 ml)
  2. washThe extract was washed with 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 (1:4-1:1)
  6. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-713dc69065924deab136cbe1de1cec06
Source dataset
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09221836B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes