Cesium carbonate → 3-[4-(2-Morpholin-4-yl-ethoxy)-phenylamino]-phthalic acid dimethyl ester

HRID 448394

반응식

HRID 448394 반응식
[N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:17][O:18][C:19](=[O:31])[C:20]1[C:21](=[C:26](I)[CH:27]=[CH:28][CH:29]=1)[C:22]([O:24][CH3:25])=[O:23].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]>[CH3:25][O:24][C:22](=[O:23])[C:21]1[C:20](=[C:29]([NH:16][C:13]2[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[CH:11][CH:12]=2)[CH:28]=[CH:27][CH:26]=1)[C:19]([O:18][CH3:17])=[O:31]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2326127Dimethyl 3-iodophthalateHCID 64847114-(2-Morpholinoethoxy)aniline

생성물 1

HCID 583073333-[4-(2-Morpholin-4-yl-ethoxy)-phenylamino]-phthalic acid dimethyl ester수율 70%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 6344Dichloromethane용매

실험 절차

A mixture of 4-(2-morpholin-4-yl-ethoxy)-phenylamine (1.4 g, 6.2 mmol), 3-iodophthalic acid dimethyl ester (2.0 g, 6.2 mmol), Pd2(dba)3 (0.26 g, 0.28 mmol), rac-BINAP (0.12 g, 0.19 mmol), and cesium carbonate (2.8 g, 8.6 mmol), in 12 mL toluene was heated to reflux under nitrogen for 16 hours. The reaction mixture was cooled, diluted with CH2Cl2 (20 mL), and filtered through Celite, and the filter was washed with additional CH2Cl2 (60 mL). The filtrate was evaporated in vacuo, and the residue was purified by ISCO silica gel flash chromatography using a methylene chloride-methanol gradient, eluting 1.8 g of the product at 95:5 methylene chloride-methanol, in 70% yield, as a pale yellow solid; 1H NMR (CDCl3) δ 3.00-3.51 (m, 6H), 3.87 (s, 3H), 3.88 (s, 3H), 4.08-4.34 (m, 4H), 4.52-4.62 (m, 2H), 6.89 (d, J=8.7 Hz, 2H), 6.99 (d, J=7.1, 1H), 7.09-7.12 (m, 3H), 7.23-7.28 (m, 1H), 8.08 (s, 1H).

후처리

  1. temperatureto reflux under nitrogen for 16 hours
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered through Celite
  4. washthe filter was washed with additional CH2Cl2 (60 mL)
  5. customThe filtrate was evaporated in vacuo
  6. customthe residue was purified by ISCO silica gel flash chromatography
  7. washeluting 1.8 g of the product at 95:5 methylene chloride-methanol

출처 및 근거

ORD 기록
ord-41db7f6487b5439ba7499b8d7a4761a8
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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