3-Chloroaniline → HCID 45376729, compound

HRID 1184529Notes

Reaction equation

HRID 1184529 reaction equation
C([O:4][C:5]1[CH:6]=[C:7](/[CH:12]=[CH:13]/[C:14]([OH:16])=O)[CH:8]=[CH:9][C:10]=1[F:11])(=O)C.S(Cl)(Cl)=O.[Cl:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][CH:28]=1)[NH2:25]>C1COCC1.C(Cl)Cl>[Cl:21][C:22]1[CH:23]=[C:24]([NH:25][C:14](=[O:16])/[CH:13]=[CH:12]/[C:7]2[CH:8]=[CH:9][C:10]([F:11])=[C:5]([OH:4])[CH:6]=2)[CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 79323-ChloroanilineHCID 24386Thionyl Chloride2×HCID 58387451HCID 58387451, compound

Product 1

HCID 45376729HCID 45376729, compoundYield 33.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

A solution (E)-3-(3-acetoxy-4-fluoro-phenyl)-acrylic acid (0.17 g, 0.76 mmol) and thionyl chloride (0.069 mL, 0.95 mmol) in dry THF (2 mL) was stirred at 55° C. for 3 hrs. Then a further aliquot of thionyl chloride (0.008 mL, 0.11 mmol) was added and the mixture was stirred at reflux temperature for additional 1.5 hrs. After cooling to about 35° C., a solution of 3-chloro-aniline (0.204 mL, 1.90 mmol) dry THF (0.5 mL) was added dropwise. After stirring at RT for 16 hrs, the reaction mixture was diluted with DCM and washed with water, aqueous hydrochloric acid, and brine. The organic layer was then dried over sodium sulphate and evaporated. The resulting raw material was taken up without further purification with THF (2 mL), and a 3N methanolic solution of hydrochloric acid (4 mL-12 mmols) was added to the so obtained solution. The resulting mixture was stirred at RT for 16 hrs, concentrated under reduced pressure, taken up with solvent an re-evaporated (3 times with MeOH and once with acetone) to give a light yellow residue that was sequentially triturated with toluene, ethyl ether and dichlorometane. After the last filtration and drying, 75 mg of the title (E)-N-(3-chloro-phenyl)-3-(4-fluoro-3-hydroxy-phenyl)-acrylamide were obtained, as a light yellow powder.

Workup

  1. temperatureat reflux temperature for additional 1.5 hrs
  2. stirringAfter stirring at RT for 16 hrs
  3. washwashed with water, aqueous hydrochloric acid, and brine
  4. dry with materialThe organic layer was then dried over sodium sulphate
  5. customevaporated
  6. customThe resulting raw material was taken up without further purification with THF (2 mL)
  7. additiona 3N methanolic solution of hydrochloric acid (4 mL-12 mmols) was added to the so obtained solution
  8. stirringThe resulting mixture was stirred at RT for 16 hrs
  9. concentrationconcentrated under reduced pressure
  10. customan re-evaporated (3 times with MeOH
  11. customonce with acetone) to give a light yellow residue that
  12. customwas sequentially triturated with toluene, ethyl ether and dichlorometane
  13. filtrationAfter the last filtration
  14. customdrying

Sources & evidence

ORD record
ord-17da6b230d284b71b5ff5233a35dacbd
Source dataset
uspto-grants-2014_03
Patent number
US08669261B2

Reaction notes

Loading…