1,4-Dioxane → 4-(Difluoromethoxy)-2-aminophenol

A mixture of 4-(difluoromethoxy)-2-nitrophenol (D94, 450 mg, 1.974 mmol), Raney-nickel (est. 200 mg), 1,4-dioxane (10 mL) and water (5 mL) was stirred at room temperature in a hydrogen atmosphere for 20 h. The reaction mixture was filtered through kieselguhr under an argon atmosphere and evaporated to dryness. The unreacted starting material was sufficiently volatile that most of it was removed by using a rotary evaporator. The residue was purified by flash column chromatography on a pre-packed silica cartridge (column size 50 g), eluting with 0-30% ethyl acetate in hexane, followed by 10-50% 2 M ammonia in methanol in DCM. The residue was further purified on an IST SCX-2 cartridge 20 g, washing with methanol (125 mL) and eluting with 2 M ammonia in methanol (125 mL). The basic eluent was evaporated to dryness to afford the desired product (D95) as a brown solid (200 mg). (M+H)+=176.

1. filtrationThe reaction mixture was filtered through kieselguhr under an argon atmosphere
2. customevaporated to dryness
3. customwas removed
4. customa rotary evaporator
5. customThe residue was purified by flash column chromatography on a pre-packed silica cartridge (column size 50 g)
6. washeluting with 0-30% ethyl acetate in hexane
7. customThe residue was further purified on an IST SCX-2 cartridge 20 g
8. washwashing with methanol (125 mL)
9. washeluting with 2 M ammonia in methanol (125 mL)
10. customThe basic eluent was evaporated to dryness

ORD record

ord-24401b508fb746859bec2a86ace7d999

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426443B2