Cesium carbonate → 3-(4-Dimethylaminomethyl-2-methoxyphenylamino)phthalic acid dimethyl ester

HRID 448371Notes

Reaction equation

HRID 448371 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]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([NH2:26])=[C:22]([O:27][CH3:28])[CH:21]=1)[CH3:18].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:26][C:23]2[CH:24]=[CH:25][C:20]([CH2:19][N:17]([CH3:16])[CH3:18])=[CH:21][C:22]=2[O:27][CH3:28])[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 220462864-((Dimethylamino)methyl)-2-methoxyaniline

Product 1

HCID 583072913-(4-Dimethylaminomethyl-2-methoxyphenylamino)phthalic acid dimethyl esterYield 78%

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), 4-dimethylaminomethyl-2-methoxyphenylamine (0.56 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 0.9 g of the product at 92:8 methylene chloride-methanol, in 78% yield: 1H NMR (CDCl3) δ 2.31 (s, 6H), 3.47 (s, 2H), 3.87 (s, 3H), 3.88 (s, 3H), 3.90 (s, 3H), 6.80 (dd, J=8.0 Hz, J=1.4 Hz, 1H), 6.99 (s, 1H), 7.14 (dd, J=7.3 Hz, J=0.9 Hz, 1H), 7.20 (d, J=8.0 Hz, 1H), 7.31 (t, J=7.9 Hz, 1H), 7.45 (dd, J=8.5 Hz, J=0.9 Hz, 1H), 7.99 (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 0.9 g of the product at 92:8 methylene chloride-methanol

Sources & evidence

ORD record
ord-2415a64aa76940e5a73a138c21a5bfbd
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

Loading…