Pyridine → Benzisothiazole

To a solution of o-toluidine (10 g, 93.4 mmol) in 50 mL toluene was added SOCl2 (12.1 g, 102 mmol) dropwise at 0° C. After the addition was complete, the reaction mixture was heated to reflux and stirred overnight. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure to give a yellow oil. The oil was dissolved in toluene (100 mL), then a solution of N-sulfinylmethanesulfonamide (20.6 g, 146 mmol) was added dropwise, followed by pyridine (7.3 g, 93.4 mmol). The mixture was heated to reflux and stirred at that temperature overnight. Toluene was then removed under reduced pressure, the residue was dissolved in EtOAc (200 mL) and washed with water (2×200 mL). The organic layer was washed with brine, dried and evaporated to give the crude product. The crude product was purified by column chromatography (3% EtOAc/PE) to afford 6.2 g title compound as colorless oil. 1H NMR (CHLOROFORM-d) δ 9.22 (s, 1H), 7.88 (d, J=9.7 Hz, 1H), 7.80 (d, J=8.6 Hz, 1H), 7.46 (ddd, J=8.9, 6.5, 1.2 Hz, 1H), 7.26 (dd, J=7.9, 6.6 Hz, 1H).

1. additionAfter the addition
2. temperaturethe reaction mixture was heated
3. temperatureto reflux
4. concentrationconcentrated under reduced pressure
5. customto give a yellow oil
6. temperatureThe mixture was heated
7. temperatureto reflux
8. stirringstirred at that temperature overnight
9. customToluene was then removed under reduced pressure
10. dissolutionthe residue was dissolved in EtOAc (200 mL)
11. washwashed with water (2×200 mL)
12. washThe organic layer was washed with brine
13. customdried
14. customevaporated
15. customto give the crude product
16. customThe crude product was purified by column chromatography (3% EtOAc/PE)

ORD record

ord-9b356efddad846179c50c8da1900a751

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108921B2