Cesium carbonate → N-(4-(benzylthio)-2-nitrophenyl)-4-bromo-5-fluoro-2-methoxyaniline

HRID 1504551

反応式

HRID 1504551 の反応式
[CH2:1]([S:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[C:11]([N+:16]([O-:18])=[O:17])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:19][C:20]1[CH:25]=[C:24]([O:26][CH3:27])[C:23](I)=[CH:22][C:21]=1[F:29].COC1CCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:1]([S:8][C:9]1[CH:15]=[CH:14][C:12]([NH:13][C:23]2[CH:22]=[C:21]([F:29])[C:20]([Br:19])=[CH:25][C:24]=2[O:26][CH3:27])=[C:11]([N+:16]([O-:18])=[O:17])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

8

反応物 4

HCID 10796Cesium carbonate2 回HCID 138539Cyclopentyl methyl etherHCID 135509934-(Benzylthio)-2-nitroanilineHCID 716561571-Bromo-2-fluoro-4-iodo-5-methoxybenzene

生成物 1

HCID 117736972N-(4-(benzylthio)-2-nitrophenyl)-4-bromo-5-fluoro-2-methoxyaniline収率 104.5%

試薬・触媒・溶媒 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒

実験手順

A RBF was charged with 4-(benzylthio)-2-nitroaniline (13.72 g, 47.4 mmol), 1-bromo-2-fluoro-4-iodo-5-methoxybenzene (17.27 g, 52.2 mmol), Xantphos (1.372 g, 2.372 mmol), Pd2(dba)3 (1.086 g, 1.186 mmol), CPME (95 ml) and cesium carbonate (23.18 g, 71.2 mmol) were added. A reflux condenser was attached and the flask was lowered into a 90° C. heating bath. The mixture was stirred overnight. In the morning, the solid was scraped of the bottom of the flask, and an additional portion of cesium carbonate (23.18 g, 71.2 mmol) was added. The flask was returned to the heat with vigorous stirring for 3 h. After cooling, the mixture was diluted with EtOAc and filtered through celite with the aid of EtOAc. The filtrate was concentrated, and the residue was dissolved in DCM and loaded onto a pre-equilibrated 340-g SNAP Ultra column. The column was eluted with 0-30% EtOAc/Heptane. The material crashed out on the column, so the elution was changed to 0-50% EtOAc/Heptane with 10% DCM. The eluent was raised to 100% EtOAc, 20% DCM. Fractions containing product were combined and concentrated to give 22.96 g (>100% yield) of N-(4-(benzylthio)-2-nitrophenyl)-4-bromo-5-fluoro-2-methoxyaniline as a red solid that was 80-90% pure by LCMS. m/z (ESI) 563.0 (M+H)+.

後処理

  1. additionwere added
  2. customA reflux condenser was attached
  3. customwas lowered into a 90° C.
  4. temperatureheating bath
  5. temperatureheat
  6. stirringwith vigorous stirring for 3 h
  7. temperatureAfter cooling
  8. filtrationfiltered through celite with the aid of EtOAc
  9. concentrationThe filtrate was concentrated
  10. dissolutionthe residue was dissolved in DCM
  11. washThe column was eluted with 0-30% EtOAc/Heptane
  12. washso the elution
  13. temperatureThe eluent was raised to 100% EtOAc, 20% DCM
  14. additionFractions containing product
  15. concentrationconcentrated

出典と根拠

ORDレコード
ord-c02b1c34837643deb339989b54bb0f20
出典データセット
uspto-grants-2015_12
特許番号
US09212182B2

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