Cesium carbonate → HCID 58307247, compound

HRID 448365Notes

Reaction equation

HRID 448365 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]([CH3:30])[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]

Participants

8

Reactant 4

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

Product 1

HCID 58307247HCID 58307247, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e4857c6bb2a94111b88bf962e02e1f1f
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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