Methane → (4s,7r)-2-(3,5-Dichloro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

Temperature

95 °C

A mixture of (4S,7R)-2-(3,5-dichloro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 45; 200 mg, 0.59 mmol) and iodomethane (180 μL, 2.9 mmol) in dimethylformamide (3 mL) was heated at 95° C. for 7 h and then stirred overnight at room temperature. The solvent was evaporated, dichloromethane (50 mL) was added and the solution was washed with water (3×25 mL), saturated aqueous sodium thiosulfate (25 mL), and brine (25 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 20% ethyl acetate/petroleum ether, and dried under high vacuum overnight to give a pale orange solid. This was dissolved in ethanol and the solution was treated with charcoal, then filtered through Celite (washing the Celite well with ethanol) and evaporated to give a brown solid. The brown solid was dissolved in ethyl ether and the solution was cooled in a freezer for 1 h. The solid was filtered off and washed with ether to give (4S,7R)-2-(3,5-dichloro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (39 mg, 19%). ES(+)-MS (M+H) 351.

1. customThe solvent was evaporated
2. additiondichloromethane (50 mL) was added
3. washthe solution was washed with water (3×25 mL), saturated aqueous sodium thiosulfate (25 mL), and brine (25 mL)
4. dry with materialThe solution was dried (magnesium sulfate)
5. filtrationfiltered
6. customevaporated
7. custompurified by column chromatography
8. washeluting with 20% ethyl acetate/petroleum ether
9. customdried under high vacuum overnight
10. customto give a pale orange solid
11. filtrationfiltered through Celite (
12. washwashing the Celite well with ethanol) and
13. customevaporated
14. customto give a brown solid
15. temperaturethe solution was cooled in a freezer for 1 h
16. filtrationThe solid was filtered off
17. washwashed with ether

ORD record

ord-3112dfb884d2483582ed7882a1b6c25a

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622492B2