3,4-Difluorobenzene-1-sulfonyl chloride → 1-{1-[(3,4-Difluorophenyl)sulfonyl]-5-phenyl-1H-pyrrol-3-yl}-N-methylmethanamine hydrochloride

To a solution (7 mL) of tert-butyl methyl[(5-phenyl-1H-pyrrol-3-yl)methyl]carbamate (70 mg) in tetrahydrofuran was added tert-butoxy potassium (42 mg) at room temperature and the mixture was stirred for 30 min. 3,4-Difluorobenzenesulfonyl chloride (68 mg) was added at room temperature and the mixture was stirred for 1.5 hr. To the reaction mixture was added ice water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→4:1), and dissolved in methanol (15 mL). 4 mol/l Hydrogen chloride-ethyl acetate solution (1.5 mL) was added and the mixture was stirred at 65° C. for 30 min. The reaction mixture was concentrated under reduced pressure, and crystallized from ethyl acetate to give the title compound as pale-brown crystals (yield 32 mg, 33%).

1. stirringthe mixture was stirred for 1.5 hr
2. extractionthe mixture was extracted with ethyl acetate
3. washThe extract was washed with saturated brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→4:1)
7. dissolutiondissolved in methanol (15 mL)
8. addition4 mol/l Hydrogen chloride-ethyl acetate solution (1.5 mL) was added
9. stirringthe mixture was stirred at 65° C. for 30 min
10. concentrationThe reaction mixture was concentrated under reduced pressure
11. customcrystallized from ethyl acetate

ORD record

ord-323a68e15b264fa1b1ca4f59e1f99bc8

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08048909B2