Hydrochloric Acid → HCID 57941481, compound

Temperature

0 °C

Triethylamine (0.38 mL, 2.73 mmol) was added dropwise to a cooled (0° C.) solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 330 mg, 1.54 mmol) in 1,2-dichloroethane (4 mL) over 1 min. A solution of N′-(3-isopropyl-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (142 mg, 0.54 mmol) in 1,2-dichloroethane (8 mL) was added. The reaction mixture was stirred at 0° C. for 15 min, at room temperature for 15 min, and then in an oil bath at 50° C. for 1 h. The reaction mixture was cooled. A solution of HCl in dioxane (4 M; 5 mL, 20 mmol) was added and the mixture was heated in an oil bath at 100° C. for 1 h and allowed to cool. Dichloromethane (100 mL) was added and the mixture was washed with 1:1 water/brine (20 mL), dried (magnesium sulfate), filtered, evaporated, and purified by flash chromatography, eluting with 50% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and then co-evaporated with methanol and then diethyl ether. The residue was dried under high vacuum at 70° C. overnight to give (4S,7R)-2-(3-isopropyl-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (51 mg, 29%) as a pale yellow solid. ES(+)-MS (M+H) 325.

1. waitin an oil bath at 50° C. for 1 h
2. temperatureThe reaction mixture was cooled
3. temperaturethe mixture was heated in an oil bath at 100° C. for 1 h
4. temperatureto cool
5. washthe mixture was washed with 1:1 water/brine (20 mL)
6. dry with materialdried (magnesium sulfate)
7. filtrationfiltered
8. customevaporated
9. custompurified by flash chromatography
10. washeluting with 50% ethyl acetate/hexanes
11. customFractions homogeneous for the product were evaporated
12. customThe residue was dried under high vacuum at 70° C. overnight

ORD record

ord-28431f2057ff43e5b13b26dbd3b32a79

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622492B2