Hydrochloric Acid → HCID 16116996, compound

HRID 1438046Notes

Reaction equation

HRID 1438046 reaction equation
C(N(CC)CC)C.[CH3:8][C@:9]12[C:15]([CH3:17])([CH3:16])[C@H:12]([CH2:13][CH2:14]1)[CH:11]([C:18](Cl)=[O:19])[C:10]2=O.C(O[C:27]([N:29](C)[NH:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=1[Cl:38])=O)(C)(C)C.Cl.O1CCOCC1>ClCCCl.ClCCl>[Cl:38][C:32]1[C:33]([Cl:37])=[CH:34][CH:35]=[CH:36][C:31]=1[N:30]1[C:18](=[O:19])[C:11]2[C@@H:12]3[C:15]([CH3:17])([CH3:16])[C@@:9]([CH3:8])([CH2:14][CH2:13]3)[C:10]=2[N:29]1[CH3:27]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 57941306(1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride2×HCID 57941309HCID 57941309, compound

Product 1

HCID 16116996HCID 16116996, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (1.3 mL, 9.33 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; 905 mg, 4.22 mmol) in 1,2-dichloroethane (8 mL) over 1 min. A solution of N′-(2,3-dichloro-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (775.8 mg, 2.66 mmol) in 1,2-dichloroethane (14 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 30 min. The reaction mixture was cooled. A solution of HCl in dioxane (4 M; 10 mL, 40 mmol) was added and the mixture was heated at reflux for 1 h and allowed to cool. Dichloromethane (150 mL) was added and the mixture was washed with 1:1 water/brine (30 mL), dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO 120 g column, eluting with 20-100% 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-(2,3-dichloro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (332 mg, 36%) as a white solid. ES(+)-MS (M+H) 351.

Workup

  1. waitin an oil bath at 50° C. for 30 min
  2. temperatureThe reaction mixture was cooled
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 1 h
  5. temperatureto cool
  6. washthe mixture was washed with 1:1 water/brine (30 mL)
  7. dry with materialdried (magnesium sulfate)
  8. filtrationfiltered
  9. customevaporated
  10. custompurified
  11. washeluting with 20-100% ethyl acetate/hexanes
  12. customFractions homogeneous for the product were evaporated
  13. customThe residue was dried under high vacuum at 70° C. overnight

Sources & evidence

ORD record
ord-7ec072045985495aba8e725dbcc9c98e
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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