Hydrochloric Acid → 3-(2,2-dimethyl4-oxo4H-1,3-benzodioxin-5-yl)-benzoic acid, ethyl ester

HRID 1583103Notes

Reaction equation

HRID 1583103 reaction equation
[CH3:1][C:2]1([CH3:21])[O:7][C:6]2[CH:8]=[CH:9][CH:10]=[C:11](OS(C(F)(F)F)(=O)=O)[C:5]=2[C:4](=[O:20])[O:3]1.[CH2:22]([O:24][C:25]([C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1)=[O:26])[CH3:23].C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][C:2]1([CH3:21])[O:7][C:6]2[CH:8]=[CH:9][CH:10]=[C:11]([C:31]3[CH:32]=[C:27]([CH:28]=[CH:29][CH:30]=3)[C:25]([O:24][CH2:22][CH3:23])=[O:26])[C:5]=2[C:4](=[O:20])[O:3]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 3249312(3-Ethoxycarbonylphenyl)boronic acidHCID 108927482,2-Dimethyl-4-oxo-4H-benzo[D][1,3]dioxin-5-YL trifluoromethanesulfonate

Product 1

HCID 207287193-(2,2-dimethyl4-oxo4H-1,3-benzodioxin-5-yl)-benzoic acid, ethyl esterYield 63.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,2-dimethyl-5-trifluoromethane-sulfonyloxy-4H-1,3-benzodioxin-4-one (2.0 g, 5.8 mmol), 3-ethoxycarbonylphenylboronic acid (1.34 g, 6.9 mmol) and anhydrous K2CO3 powder (2.61 g, 18.9 mmol) in DMF (30 mL) was added tetrakis(triphenylphosphine)palladium (0.202 g, 0.175 mmol). The mixture was heated at reflux for 2 h. The reaction mixture was allowed to cool to room temperature (“rt”) and 1 N HCl (25 mL) was added. The mixture was extracted with EtOAc (3×25 mL). The combined extracts were washed with water and brine, then dried over MgSO4, filtered, and concentrated. The crude material was purified by flash chromatography (1:15 EtOAc/hexanes) to afford 3-(2,2-dimethyl4-oxo4H-1,3-benzodioxin-5-yl)-benzoic acid, ethyl ester (1.2 g, 63%) as a white solid: 1H NMR (CDCl3) δ1.39 (t, J=7.1 Hz, 3H), 1.80 (s, 6H), 4.39 (q, J=7.0 Hz, 2H), 7.01 (d, J=8.0 Hz, 2H), 7.47-7.57 (m, 3H), 8.00 (t, J=1.5 Hz, 1H) 8.07 (dt, J=7.5, 1.5 Hz, 1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2 h
  3. additionwas added
  4. extractionThe mixture was extracted with EtOAc (3×25 mL)
  5. washThe combined extracts were washed with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by flash chromatography (1:15 EtOAc/hexanes)

Sources & evidence

ORD record
ord-3935e5feb05e49059d70b81c03116796
Source dataset
uspto-grants-2004_05
Patent number
US06740777B2

Reaction notes

Loading…