Methanol → N-[3,4-bis(difluoromethoxy)benzyl]-2-methylpropane-2-sulfinamide

To a solution of 3,4-bis(difluoromethoxy)benzaldehyde (10-2, 100 mg, 0.42 mmol, 1 equiv) in THF (840 uL) was added 2-methylpropane-2-sulfinamide (56 mg, 0.46 mmol, 1.1 equiv) and titanium ethoxide (440 uL, 2.10 mmol, 5.0 equiv), and the reaction mixture stirred at ambient temperature for 4.5 hours. The reaction mixture was then cooled to 0° C. and sodium borohydride (31.8 mg, 0.84 mmol, 2.0 equiv) was added portionwise and the reaction was stirred for an additional hour. Methanol (2 mL) was added slowly and the reaction mixture was partitioned between EtOAc (20 mL) and brine (20 mL) and filtered. The organic phase was dried over MgSO4 and concentrated to afford crude N-[3,4-bis(difluoromethoxy)benzyl]-2-methylpropane-2-sulfinamide, which was dissolved in methanol (2.2 mL). To the solution was added HCl (2 M in ether, 655 uL, 3 equiv), and the reaction mixture stirred for 30 minutes. It was then concentrated to afford the desired product (10-3) as a white solid. ESI+MS [M-NH2]+ C9H7F4O2: 223.0 found, 223.0 required.

1. temperatureThe reaction mixture was then cooled to 0° C.
2. stirringthe reaction was stirred for an additional hour
3. customthe reaction mixture was partitioned between EtOAc (20 mL) and brine (20 mL)
4. filtrationfiltered
5. dry with materialThe organic phase was dried over MgSO4
6. concentrationconcentrated

ORD record

ord-cb4445aa037b441e9ae695374aa4292f

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08003797B2