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

HRID 1865111노트

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HRID 1865111 반응식
[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]

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 31268PyrrolidineHCID 57974728HCID 57974728, 화합물

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 634876Binap, (A+-)-촉매HCID 1140Toluene용매

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온도
100 °C

실험 절차

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)

후처리

  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

출처 및 근거

ORD 기록
ord-46532263e2a14589a4f8816393ac5da6
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07625932B2

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