2,5-Dimethoxyaniline → HCID 58307300, compound

HRID 448354Notes

Reaction equation

HRID 448354 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][O:17][C:18]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:19]=1[NH2:20].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:20][C:19]2[CH:21]=[C:22]([O:25][CH3:26])[CH:23]=[CH:24][C:18]=2[O:17][CH3:16])[CH:11]=[CH:12][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7]

Participants

8

Reactant 4

HCID 76132,5-DimethoxyanilineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2326127Dimethyl 3-iodophthalate

Product 1

HCID 58307300HCID 58307300, compoundYield 68%

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), 2,5-dimethoxyaniline (0.48 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 hexanes-ethyl acetate gradient, eluting 0.73 g of the product at 80:20 hexanes-ethyl acetate, in 68% yield: 1H NMR (CDCl3) δ 3.74 (s, 3H), 3.85 (s, 3H), 3.88 (s, 3H), 3.89 (s, 3H), 6.48 (dd, J=8.8 Hz, J=2.9 Hz, 1H), 6.83 (d, J=8.8 Hz, 1H), 6.87 (d, J=2.9 Hz, 1H), 7.19 (dd, J=7.7 Hz, J=0.9 Hz, 1H), 7.34 (t, J=7.9 Hz, 1H), 7.55 (dd, J=8.5 Hz, J=0.9 Hz, 1H), 7.95 (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 0.73 g of the product at 80:20 hexanes-ethyl acetate

Sources & evidence

ORD record
ord-394632b252c64465b9468c742ec85e51
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

Loading…