Formaldehyde → 4-[(4-Chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)-1-methylpiperidine

To dichloromethane (5 ml) were added 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)piperidine hydrochloride (100 mg, 0.245 mmol), triethylamine (0.070 ml, 0.50 mmol) and a 37% aqueous formaldehyde solution (0.060 ml, 0.739 mmol), followed by the addition of sodium triacetoxyborohydride (220 mg, 1.04 mmol) at room temperature. After stirring at room temperature for 14 hours, a 1N aqueous sodium hydroxide solution (6.0 ml) was added. The mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added diethyl ether and the mixture was washed with a 1N aqueous sodium hydroxide solution. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue thus obtained was subjected to flash silica gel chromatography, and the fraction obtained from the dichloromethane:methanol=30:1 eluate was concentrated under reduced pressure to give a white solid. The solid thus obtained was washed with diisopropyl ether, whereby the title compound (70 mg, 0.18 mmol, 74%) was obtained as a white powder.

1. stirringThe mixture was stirred at room temperature for 30 minutes
2. washthe mixture was washed with a 1N aqueous sodium hydroxide solution
3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
4. filtrationAfter filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. customThe residue thus obtained
7. concentrationmethanol=30:1 eluate was concentrated under reduced pressure
8. customto give a white solid
9. customThe solid thus obtained

ORD record

ord-d2635380630d4519a0d10fa4846b551c

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07399775B2