Hydrochloric Acid → HCID 57941336, compound

Temperature

0 °C

Triethylamine (1.1 mL, 7.9 mmol) was added dropwise to a cooled (0° C.) solution of N′-(3-fluoro-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (380 mg, 1.58 mmol) in 1,2-dichloroethane (8 mL) over 1 min. A solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 980 mg, 4.56 mmol) in 1,2-dichloroethane (16 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 2 h. The reaction mixture was cooled. A solution of HCl in dioxane (4 M; 8 mL, 32 mmol) was added and the mixture was heated in an oil bath at 100° C. for 1 h. Dichloromethane (100 mL) was added and the mixture was washed with 1:1 water/brine (20 mL), dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO 40 g column, eluting with 20-50% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and then co-evaporated with dichloromethane and then petroleum ether. The residue was dried under high vacuum at 70° C. overnight to give (4S,7R)-2-(3-fluoro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (130 mg, 27%) as an off-white solid. ES(+)-MS (M+H) 301.

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

ORD record

ord-fe1f18d4d0cc4490999136dfb9da2d94

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622492B2