Methyl iodide → HCID 57941434, compound

Temperature

100 °C

A mixture of (4S,7R)-2-(4-hydroxy-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 41; 1.60 g, 5.6 mmol) and iodomethane (1.1 mL, 17.7 mmol) in dimethylformamide (50 mL) was heated in a sealed tube at about 100° C. for 2.5 h. The reaction mixture was allowed to cool to room temperature. The tube was carefully opened, and the contents were allowed to stand at room temperature over a weekend. The solvent was evaporated and dichloromethane (250 mL) was added. The solution was washed with water (100 mL), saturated sodium thiosulfate (100 mL), water (100 mL), and brine (100 mL). The organic layer was dried (magnesium sulfate), filtered, and evaporated. The residue was triturated with ethyl acetate and the solid was filtered off and washed with 20% ethyl acetate/hexanes and then hexanes, and then purified using a Biotage 40M system, eluting with 3-5% methanol/dichloromethane to give (4S,7R)-2-(4-Hydroxy-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (1.26 g, 75%) as a light yellow solid. APCI(+)-MS (M+H) 299.

1. temperatureto cool to room temperature
2. waitto stand at room temperature over a weekend
3. customThe solvent was evaporated
4. additiondichloromethane (250 mL) was added
5. washThe solution was washed with water (100 mL), saturated sodium thiosulfate (100 mL), water (100 mL), and brine (100 mL)
6. dry with materialThe organic layer was dried (magnesium sulfate)
7. filtrationfiltered
8. customevaporated
9. customThe residue was triturated with ethyl acetate
10. filtrationthe solid was filtered off
11. washwashed with 20% ethyl acetate/hexanes
12. customhexanes, and then purified
13. washeluting with 3-5% methanol/dichloromethane

ORD record

ord-08a0f9071193430daf04eaae5b2476c0

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622492B2