Hydrochloric Acid → (1R)-N-[3(trifluoromethyl)-4-fluorophenyl]-1,8,8-trimethyl-2,4-dioxobicyclo [3.2.1]octane-3-carboxamide

To an ice-cooled solution of (1R)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione (0.18 g, 1.0 mmole), triethylamine (0.10 g, 1.0 mmole) and 4-(dimethylamino)pyridine (0.12 g, 1.0 mmole) in dry dichloromethane (25 mL) was added a solution of 4-fluoro-3-(trifluoromethyl)phenyl isocyanate (0.21 g, 1.0 mmole) in dry dichloromethane (5 mL). The resulting reaction mixture was allowed to stir overnight under a nitrogen atmosphere, during which time it came up to room temperature. It was then stirred at 30° C. for twenty-four hours. The resulting mixture was treated with 2N aqueous HCl (30 mL) and the layers were separated. The aqueous layer was extracted with two additional portions of dichloromethane (50 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator. The desired product was isolated by chromatography on silica gel (10% ethyl acetate/hexane) and recrystallized from 95% ethanol to yield the title compound as a beige solid (0.18 g, 48% yield), mp=96–98° C.; MS (−) ESI m/z=384 (M−H)−; [α]D25=+22.1° (c=1, EtOH).

1. customThe resulting reaction mixture
2. customcame up to room temperature
3. stirringIt was then stirred at 30° C. for twenty-four hours
4. customthe layers were separated
5. extractionThe aqueous layer was extracted with two additional portions of dichloromethane (50 mL)
6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
7. concentrationconcentrated on a rotary evaporator

ORD-Eintrag

ord-45f0468b09374c209663dca08aa6fc46

Quelldatensatz

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07179943B2