Cesium carbonate → 3-[2-(2-Dimethylaminoethoxy)-4-methoxyphenylamino]phthalic acid dimethyl ester

HRID 448365ノート

反応式

HRID 448365 の反応式
[CH3:1][O:2][C:3](=[O:15])[C:4]1[C:5](=[C:10](I)[CH:11]=[CH:12][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7].[CH3:16][N:17]([CH3:30])[CH2:18][CH2:19][O:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:22]=1[NH2:29].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.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(Cl)Cl.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]>[CH3:1][O:2][C:3](=[O:15])[C:4]1[C:5](=[C:10]([NH:29][C:22]2[CH:23]=[CH:24][C:25]([O:27][CH3:28])=[CH:26][C:21]=2[O:20][CH2:19][CH2:18][N:17]([CH3:16])[CH3:30])[CH:11]=[CH:12][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2326127Dimethyl 3-iodophthalateHCID 189801482-(2-Dimethylaminoethoxy)-4-methoxyphenylamine

生成物 1

HCID 583072473-[2-(2-Dimethylaminoethoxy)-4-methoxyphenylamino]phthalic acid dimethyl ester収率 20%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of 3-iodophthalic acid dimethyl ester (1.0 g, 3.1 mmol), 2-(2-dimethylaminoethoxy)-4-methoxyphenylamine (0.65 g, 3.1 mmol), Pd2(dba)3 (0.13 g, 0.14 mmol), rac-BINAP (0.058 g, 0.093 mmol), and cesium carbonate (1.4 g, 4.3 mmol), in 6 mL toluene was heated to reflux under nitrogen for 24 hours. The reaction mixture was cooled, diluted with CH2Cl2 (10 mL), and filtered through Celite, and the filter was washed with additional CH2Cl2 (30 mL). The filtrate was evaporated, and the residue was chromatographed using a methylene chloride-methanol gradient, eluting 0.82 g of the product at 95:5 methylene chloride-methanol. This material was dissolved in methylene chloride (100 mL) and extracted with dilute aqueous HCl (3×75 mL). The combined aqueous extracts were washed with methylene chloride (3×75 mL), made basic (Na2CO3), and extracted into methylene chloride (3×75 mL). The organic phases were dried (MgSO4) and evaporated, providing 0.25 g, in 20% yield: 1H NMR (CDCl3) δ 2.28 (s, 6H), 2.70 (t, J=5.8 Hz, 2H), 3.80 (s, 3H), 3.87 (s, 3H), 3.88 (s, 3H), 4.06 (t, J=5.8 Hz, 2H), 6.46 (dd, J=8.6 Hz, J=2.5 Hz, 1H), 6.54 (d, J=2.7 Hz, 1H), 7.00 (dd, J=7.3 Hz, J=1.1 Hz, 1H), 7.09-7.23 (m, 3H), 7.87 (br, 1H).

後処理

  1. temperatureto reflux under nitrogen for 24 hours
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered through Celite
  4. washthe filter was washed with additional CH2Cl2 (30 mL)
  5. customThe filtrate was evaporated
  6. customthe residue was chromatographed
  7. washeluting 0.82 g of the product at 95:5 methylene chloride-methanol
  8. dissolutionThis material was dissolved in methylene chloride (100 mL)
  9. extractionextracted with dilute aqueous HCl (3×75 mL)
  10. washThe combined aqueous extracts were washed with methylene chloride (3×75 mL)
  11. extractionextracted into methylene chloride (3×75 mL)
  12. dry with materialThe organic phases were dried (MgSO4)
  13. customevaporated
  14. customproviding 0.25 g

出典と根拠

ORDレコード
ord-e4857c6bb2a94111b88bf962e02e1f1f
出典データセット
uspto-grants-2013_07
特許番号
US08481568B2

反応ノート

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