Cesium carbonate → 1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1928638Notes

Reaction equation

HRID 1928638 reaction equation
I[C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][C@H:11]2[CH3:15])=[CH:4][CH:3]=1.[CH2:18]([O:20][C:21]([C:23]1[CH:24]=[N:25][NH:26][CH:27]=1)=[O:22])[CH3:19].CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.[Cu](I)I>[CH2:18]([O:20][C:21]([C:23]1[CH:24]=[N:25][N:26]([C:2]2[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]3[CH2:14][CH2:13][CH2:12][C@H:11]3[CH3:15])=[CH:4][CH:3]=2)[CH:27]=1)=[O:22])[CH3:19]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 57675747(2R)-1-[3-(4-iodophenoxy)propyl]-2-methylpyrrolidine

Product 1

HCID 595417211-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of (2R)-1-[3-(4-iodophenoxy)propyl]-2-methylpyrrolidine obtained in Example 1-(2) (1.60 g), 1H-pyrazole-4-carboxylic acid ethyl ester (0.779 g), (rac-trans-N,N′-dimethylcyclohexane-1,2-diamine (0.263 g), copper iodide (0.088 g) and cesium carbonate (3.02 g) in N,N-dimethylformamide (2.5 mL) was stirred at 120° C. for 4 hours. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=3:1) to give the titled compound (1.11 g) as a yellow oil.

Workup

  1. extractionextracted with ethyl acetate
  2. concentrationThe organic layer was concentrated under reduced pressure
  3. customthe resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-4728dda7e5814e889e8a888409984761
Source dataset
uspto-grants-2012_05
Patent number
US08183387B2

Reaction notes

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