Cesium carbonate → tert-butyl (3S,5R)-3-[[[1-(2-methoxy-2-oxoethyl)-1H-benzimidazol-2-yl]carbonyl](2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 1259989Notes

Reaction equation

HRID 1259989 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][C:40]([O:42][CH3:43])=[O:41].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:43][O:42][C:40](=[O:41])[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]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 58355717tert-Butyl (3S,5R)-3-{(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino)-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

Product 1

HCID 58355362tert-butyl (3S,5R)-3-[[[1-(2-methoxy-2-oxoethyl)-1H-benzimidazol-2-yl]carbonyl](2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

tert-Butyl (3S,5R)-3-{(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (1.06 g) was dissolved in dimethylformamide (20 ml), methyl bromoacetate (390 μl) and cesium carbonate (2.02 g) were added and the mixture was stirred at 55° C. 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 residue was subjected to silica gel chromatography, and a fraction eluted with ethyl acetate-hexane (1:9)-ethyl acetate was concentrated under reduced pressure to give the object product (1.19 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. washa fraction eluted with ethyl acetate-hexane (1:9)-ethyl acetate
  8. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-42da9287405c45779eb5d4679d5b0ceb
Source dataset
uspto-grants-2013_06
Patent number
US08466282B2

Reaction notes

Loading…