Cesium carbonate → HCID 58307320, compound

HRID 448391Notes

Reaction equation

HRID 448391 reaction equation
[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]([CH3:35])[CH2:18][CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:22]=1.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:27][C:24]2[CH:25]=[CH:26][C:21]([O:20][CH2:19][CH2:18][N:17]([CH3:35])[CH3:16])=[CH:22][C:23]=2[O:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:11]=[CH:12][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2326127Dimethyl 3-iodophthalateHCID 58307289HCID 58307289, compound

Product 1

HCID 58307320HCID 58307320, compoundYield 76%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-iodophthalic acid dimethyl ester (2.0 g, 6.2 mmol), 4-(2-dimethylamino-ethoxy)-2-phenoxy-phenylamine (1.9 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 2.2 g of the product, an orange solid, at 95:5 methylene chloride-methanol, in 76% yield; 1H NMR (CDCl3) δ 2.31 (s, 6H), 2.69 (t, J=5.6 Hz, 2H), 3.74 (s, 3H), 3.84 (s, 3H), 3.99 (t, J=5.6 Hz, 2H), 6.61 (d, J=2.6 Hz, 1H), 6.69 (dd, J=8.5 Hz, J=2.8 Hz, 1H), 6.86-6.90 (m, 2H), 6.98 (dd, J=7.3 Hz, J=1.1 Hz, 1H), 7.01-7.07 (m, 1H), 7.11 (dd, J=8.6 Hz, J=1.1 Hz, 1H), 7.22-7.30 (m, 4H), 7.85 (s, 1H).

Workup

  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 2.2 g of the product

Sources & evidence

ORD record
ord-ed51515294ce4d81bb34e2af61109989
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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