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

HRID 448397Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 448397
[N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:11]=[C:12]([NH2:16])[CH:13]=[CH:14][CH:15]=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:12]2[CH:13]=[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]=2)[CH:28]=[CH:27][CH:26]=1)[C:19]([O:18][CH3:17])=[O:31]

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2326127Dimethyl 3-iodophthalateHCID 64866163-(2-Morpholin-4-ylethoxy)aniline

Produkt 1

HCID 583071533-[3-(2-Morpholin-4-yl-ethoxy)-phenylamino]-phthalic acid dimethyl esterAusbeute 73 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 3-(2-morpholin-4-yl-ethoxy)-phenylamine (1.4 g, 6.1 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 1.9 g of the product at 95:5 methylene chloride-methanol, in 73% yield; 1H NMR (CDCl3) δ 2.57 (t, J=4.6 Hz, 4H), 2.79 (t, J=5.7 Hz, 2H), 3.73 (t, J=4.6 Hz, 4H), 3.87 (s, 3H), 3.89 (s, 3H), 4.09 (t, J=5.7 Hz, 2H), 6.60 (dd, J=8.0 Hz, J=2.0 Hz, 1H), 6.70 (t, J=2.1 Hz, 1H), 6.74 (dd, J=7.8 Hz, J=1.8 Hz, 1H), 7.11 (dd, J=7.4 Hz, J=1.0 Hz, 1H), 7.21 (t, J=8.1 Hz, 1H), 7.31 (t, J=8.0 Hz, 1H), 7.43 (dd, J=8.4 Hz, J=0.9 Hz, 1H), 7.98 (s, 1H).

Aufarbeitung

  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 1.9 g of the product at 95:5 methylene chloride-methanol

Quellen und Nachweise

ORD-Eintrag
ord-0bac738177a1478c97fca1a32fe4c956
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481568B2

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