3-Chloroaniline → (E)-N-(3-Chloro-phenyl)-3-(3-hydroxy-phenyl)-acrylamide
Reaction equation
[OH:1][C:2]1[CH:3]=[C:4](/[CH:8]=[CH:9]/[C:10]([OH:12])=O)[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.[Cl:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=1)[NH2:21].C(N(CC)CC)C>C1COCC1.C(Cl)Cl>[Cl:17][C:18]1[CH:19]=[C:20]([NH:21][C:10](=[O:12])/[CH:9]=[CH:8]/[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([OH:1])[CH:3]=2)[CH:22]=[CH:23][CH:24]=1Participants
Conditions
- Temperature
- 5 °C
Procedure
A solution of (E)-3-(3-hydroxy-phenyl)-acrylic acid (1.0 g, 6.1 mmol) and thionyl chloride (0.53 mL, 7.32 mmol) in dry THF (15 mL) was stirred at 55° C. for 3 hrs. Then a further aliquot of thionyl chloride (0.1 mL, 1.38 mmol) is added and the mixture is stirred at reflux temperature for additional 1.5 hrs. After cooling to about 5° C., a solution of 3-chloro-aniline (0.65 mL, 6.1 mmol) and triethylamine (3.4 mL, 24.4 mmol) in dry THF (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 dried over sodium sulphate and evaporated. The resulting raw material was purified first by column chromatography (eluant petroleum ether/AcOEt 45/55) and then by trituration in DCM, yielding 140 mg of the title compound as a white solid.
Workup
- temperatureat reflux temperature for additional 1.5 hrs
- stirringAfter stirring at RT for 16 hrs the reaction mixture
- washwashed with water, aqueous hydrochloric acid, and brine
- dry with materialThe organic layer was dried over sodium sulphate
- customevaporated
- customThe resulting raw material was purified first by column chromatography (eluant petroleum ether/AcOEt 45/55)
Sources & evidence
- ORD record
- ord-0c949cdbc3e14b8a9a402266e438d3ca
- Source dataset
- uspto-grants-2013_06
- Patent number
- US08470831B2
Reaction notes
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