Water → Methyl 3-acetyl-4-aminobenzoate

HRID 2079989Notes

Reaction equation

HRID 2079989 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[C:6](I)[CH:5]=1.C([Sn](CCCC)(CCCC)[C:18]([O:20]CC)=[CH2:19])CCC.O>C1(C)C=CC=CC=1.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][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[C:6]([C:18](=[O:20])[CH3:19])[CH:5]=1

Participants

6

Reactant 3

HCID 962WaterHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 4104649Methyl 4-amino-3-iodobenzoate

Product 1

HCID 10856336Methyl 3-acetyl-4-aminobenzoateYield 81.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

To a solution of 4-amino-3-iodo-benzoic acid methyl ester (11.30 g, 40.77 mmol) in toluene (300 mL) were added tributyl(1-ethoxyvinyl)tin (16.5 mL, 48.9 mmol) and tetrakis(triphenylphosphine)palladium(0) (9422 mg, 8.154 mmol) under nitrogen atmosphere, and the solution was stirred at 105° C. for 7 hours. After cooling to room temperature, water was added, the mixture was extracted with ethyl acetate-tetrahydrofuran, the organic layer was washed with water, and then, evaporated. The residue was dissolved in 280 mL of tetrahydrofuran, 2N hydrochloric acid (80 mL) was added thereto, followed by stirring for 3 hours at room temperature. The reaction mixture was cooled on an ice bath, an aqueous solution of 2N sodium hydroxide (80 mL) was added, an aqueous solution of saturated sodium bicarbonate was further added, and the solution was extracted with ethyl acetate. An aqueous solution of 10% potassium fluoride was added to the organic layer, and the solution was stirred for 3 hours at room temperature. The organic layer was separated, washed with brine, then evaporated, the residue was purified by silica gel column chromatography (hexane-ethyl acetate), and title compound (6.42 g, 33.2 mmol, 81.4%) was obtained.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture was extracted with ethyl acetate-tetrahydrofuran
  3. washthe organic layer was washed with water
  4. customevaporated
  5. dissolutionThe residue was dissolved in 280 mL of tetrahydrofuran
  6. addition2N hydrochloric acid (80 mL) was added
  7. stirringby stirring for 3 hours at room temperature
  8. temperatureThe reaction mixture was cooled on an ice bath
  9. additionan aqueous solution of 2N sodium hydroxide (80 mL) was added
  10. additionan aqueous solution of saturated sodium bicarbonate was further added
  11. extractionthe solution was extracted with ethyl acetate
  12. additionAn aqueous solution of 10% potassium fluoride was added to the organic layer
  13. stirringthe solution was stirred for 3 hours at room temperature
  14. customThe organic layer was separated
  15. washwashed with brine
  16. customevaporated
  17. customthe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-e6d763e59de44f74a90ba34beeea7402
Source dataset
uspto-grants-2011_04
Patent number
US07932272B2

Reaction notes

Loading…