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

HRID 448365노트

반응식

HRID 448365 반응식
[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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-e4857c6bb2a94111b88bf962e02e1f1f
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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