Hydrochloric Acid → Methanesulfonamide, N-[5-(1,1-dimethylethyl)-2-methoxy-3-nitrophenyl]-

Temperature

32.5 °C

Under N2 was charged the product of step (vii) (471 g, 2.099 mol), toluene (1880 mL) and pyridine (471 mL), then methanesulfonyl chloride (179 mL) was added dropwise over 1 h while maintaining the temperature below 35° C. The reaction was stirred at 30-35° C. overnight, before being cooled to below 20° C., then water (1880 mL) and 2 M HCl (1880 mL) were charged (pH 3 achieved). The layers were separated and the organic phase was washed with 2.5% brine (1880 mL). Heptane (3760 mL) was then charged to the organic layer over 0.5 h to isolate a precipitate. The mixture was cooled to 0° C. and stirred for 1 h. The solid was collected via vacuum filtration and washed with heptane (1880 mL), before being dried, under vacuum, at 40° C. overnight. Yield=551 g (87%). HPLC purity 98.5%. Purity >97% by 1H NMR.

1. temperaturewhile maintaining the temperature below 35° C
2. temperaturebefore being cooled to below 20° C.
3. customThe layers were separated
4. washthe organic phase was washed with 2.5% brine (1880 mL)
5. additionHeptane (3760 mL) was then charged to the organic layer over 0.5 h
6. customto isolate a precipitate
7. temperatureThe mixture was cooled to 0° C.
8. stirringstirred for 1 h
9. filtrationThe solid was collected via vacuum filtration
10. washwashed with heptane (1880 mL)
11. custombefore being dried, under vacuum, at 40° C. overnight

ORD record

ord-bf07d83a60e2434d8d49f64ed81da805

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927563B2