Methyl 3-mercaptopropionate → HCID 86641275, compound

To a mixture of 5-bromo-2-fluoroaniline (4.15 g), methyl 3-mercaptopropionate (2.62 g), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.63 g) and N,N-diisopropylethylamine (5.64 g) in 1,4-dioxane (80 mL) was added tris(dibenzylideneacetone)-dipalladium(0) (0.3 g), and the mixture was heated at reflux under an argon atmosphere overnight. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1−5/1−2/1) to give 2-fluoro-5-(2-methoxy-carbonylethylthio)aniline (4.62 g). This material was dissolved in tetrahydrofuran (120 mL). To the solution was added potassium tert-butoxide (1 mol/L tetrahydrofuran solution, 80.6 mL) at −78° C., and the mixture was stirred at the same temperature for 15 minutes. To the reaction mixture was added 1 mol/L hydrochloric acid (81 mL), and the reaction mixture was allowed to warm to room temperature, and stirred for 5 minutes. The mixture was poured into ethyl acetate, and the organic layer was separated. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1) to give the title compound (1.85 g).

1. temperaturethe mixture was heated
2. temperatureat reflux under an argon atmosphere overnight
3. customThe insoluble material was removed by filtration
4. concentrationthe filtrate was concentrated under reduced pressure
5. customThe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1−5/1−2/1)

ORD record

ord-79237e450e72456c9167083d96de6c77

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08217069B2