Methane → HCID 57941478, compound

Temperature

100 °C

A mixture of (4S,7R)-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 150 mg, 0.56 mmol), tetrabutylammonium iodide (207 mg, 0.56 mmol) and 2-bromoethyl methyl ether (540 μL, 5.75 mmol) in dimethylformamide (3 mL) was heated in an oil-bath at 100° C. for 17 h. An additional portion of 2-bromoethyl methyl ether (540 μL, 5.75 mmol) was added and the mixture was heated at 100° C. for 3 days. Dichloromethane (75 mL) and water (25 mL) were added, and the aqueous layer was back-extracted with dichloromethane (2×30 mL). The combined organic layers were washed with water (4×20 mL), aqueous sodium thiosulfate (20 mL), and brine (30 mL). The solution was dried (magnesium sulfate), filtered, evaporated and the residue was purified using an ISCO 40 g column, eluting with 20-100% ethyl acetate/hexanes to give an orange oil. This was treated with charcoal in methanol and the mixture was filtered through Celite. The solvent was evaporated to give (4S,7R)-1-(2-methoxy-ethyl)-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (10.3 mg, 6%) as an orange oil. The purity of the sample was assessed at 88% by 1H NMR. ES(+)-MS (M+H) 327.

1. temperaturethe mixture was heated at 100° C. for 3 days
2. extractionthe aqueous layer was back-extracted with dichloromethane (2×30 mL)
3. washThe combined organic layers were washed with water (4×20 mL), aqueous sodium thiosulfate (20 mL), and brine (30 mL)
4. dry with materialThe solution was dried (magnesium sulfate)
5. filtrationfiltered
6. customevaporated
7. customthe residue was purified
8. washeluting with 20-100% ethyl acetate/hexanes
9. customto give an orange oil
10. filtrationthe mixture was filtered through Celite
11. customThe solvent was evaporated

ORD record

ord-8c585314058740d7b8526465854e4a55

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622492B2