(Bromomethyl)cyclobutane → HCID 69019383, compound

Temperature

100 °C

A mixture of (bromomethyl)cyclobutane (1.7 mL, 15.1 mmol), (4R,7S)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 393 mg, 1.46 mmol) and tetra-n-butylammonium iodide (400 mg, 1.08 mmol) in N,N-dimethylformamide (7 mL) was heated in an oil-bath at 100° C. for 16 h. Additional quantities of (bromomethyl)cyclobutane (1.7 mL, 8.9 mmol) and tetra-n-butylammonium iodide (400 mg, 1.08 mmol) were added and the mixture was heated in an oil-bath at 135° C. for 6 days. The reaction mixture was allowed to cool and it was then diluted with dichloromethane (75 mL) and water (30 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (2×30 mL). The combined organic layers were washed with water (5×30 mL), sodium thiosulfate solution (30 mL) and brine (30 mL). The organic extract was dried (magnesium sulfate), filtered, evaporated, and the residue purified on an Isco 40 g column, eluting with 15-75% ethyl acetate/hexanes and then held under high vacuum to give (4R,7S)-1-(cyclobutyl)methyl-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (52 mg, 11%) as a yellow gum. ES(+)-MS (M+H) 337.

1. temperaturethe mixture was heated in an oil-bath at 135° C. for 6 days
2. temperatureto cool
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with dichloromethane (2×30 mL)
5. washThe combined organic layers were washed with water (5×30 mL), sodium thiosulfate solution (30 mL) and brine (30 mL)
6. extractionThe organic extract
7. dry with materialwas dried (magnesium sulfate)
8. filtrationfiltered
9. customevaporated
10. customthe residue purified on an Isco 40 g column
11. washeluting with 15-75% ethyl acetate/hexanes

ORD record

ord-083f9f491ab54771b10a5e7ae35893a8

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622492B2