Cesium carbonate → 4-cyano-5-ethyl-1-methyl-3-(4-pyrrolidin-1-yl-phenyl)-1H-pyrrole-2-carboxylic acid ethyl ester

HRID 1865111Notes

Reaction equation

HRID 1865111 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:29])[C:8]([CH2:27][CH3:28])=[C:9]([C:25]#[N:26])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14](OS(C(F)(F)F)(=O)=O)=[CH:13][CH:12]=1)=[O:5])[CH3:2].[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:29])[C:8]([CH2:27][CH3:28])=[C:9]([C:25]#[N:26])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[CH:13][CH:12]=1)=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 31268PyrrolidineHCID 57974728HCID 57974728, compound

Product 1

HCID 579747784-cyano-5-ethyl-1-methyl-3-(4-pyrrolidin-1-yl-phenyl)-1H-pyrrole-2-carboxylic acid ethyl esterYield 72%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Add 4-cyano-5-ethyl-1-methyl-3-(4-trifluoromethanesulfonyloxy-phenyl)-1H-pyrrole-2-carboxylic acid ethyl ester (0.3 g, 0.697 mmol, 1.0 eq, prepared in example E-97b or 97b), pyrrolidine (0.069 ml, 0.836 mmol, 1.2 eq), Pd(OAc)2 (4.69 mg, 0.0209 mmol, 0.03 eq), BINAP (19.53 mg, 0.0314 mmol, 0.045 eq) and cesium carbonate (0.318 g, 0.976 mmol, 1.4 eq) in toluene and heat at 100° C. with stirring. After 4 hours, stop reaction and let it cool down to room temperature. Partition the mixture between water and ethyl acetate. Separate the aqueous layer and extract it with ethyl acetate three times. Combine organic solution, dry over anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Purify the crude with flash chromatography eluting with 1:3 EtOAc/Hexane to provide 0.176 g (72%) of desired product as light yellow solid. Mass spectrum (m/e) 352.3 (M+1)

Workup

  1. customreaction
  2. temperaturecool down to room temperature
  3. customPartition the mixture between water and ethyl acetate
  4. customSeparate the aqueous layer
  5. extractionextract it with ethyl acetate three times
  6. dry with materialCombine organic solution, dry over anhydrous sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify the crude with flash chromatography
  10. washeluting with 1:3 EtOAc/Hexane

Sources & evidence

ORD record
ord-46532263e2a14589a4f8816393ac5da6
Source dataset
uspto-grants-2009_12
Patent number
US07625932B2

Reaction notes

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