Hydrochloric Acid → HCID 57941502, compound

HRID 1438061Notes

Reaction equation

HRID 1438061 reaction equation
[CH3:1][C@:2]12[C:8]([CH3:10])([CH3:9])[C@H:5]([CH2:6][CH2:7]1)[CH:4]([C:11](Cl)=[O:12])[C:3]2=O.C(N(CC)CC)C.C(O[C:27]([N:29](C)[NH:30][C:31]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=1[C:38]([F:41])([F:40])[F:39])=O)(C)(C)C.Cl.O1CCOCC1>ClCCCl>[F:37][C:35]1[CH:34]=[CH:33][C:32]([C:38]([F:39])([F:40])[F:41])=[C:31]([N:30]2[C:11](=[O:12])[C:4]3[C@@H:5]4[C:8]([CH3:10])([CH3:9])[C@@:2]([CH3:1])([CH2:7][CH2:6]4)[C:3]=3[N:29]2[CH3:27])[CH:36]=1

Participants

7

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 57941387HCID 57941387, compound

Product 1

HCID 57941502HCID 57941502, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

A solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 349 mg, 1.62 mmol) in 1,2-dichloroethane (9 mL) was added to a cooled (0° C.) solution of triethylamine (320 μL, 2.30 mmol) and N′-(5-fluoro-2-trifluoromethyl-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (348 mg, 1.13 mmol) in 1,2-dichloroethane (6 mL) over a period of 1 min. The reaction mixture was stirred for 10 min at room temperature and then in an oil bath at 50° C. for 1 h. A solution of HCl in dioxane (4 M; 8 mL, 32 mmol) was added and the mixture was heated at reflux for 1 h and then allowed to cool to room temperature. Silica gel was added and the solvent was evaporated. The residue was purified using an ISCO40 g column, eluting with 50-100% ethyl acetate/hexanes and then with 10% methanol/ethyl acetate. Fractions homogeneous for the product were evaporated, and the residue was dissolved in dichloromethane (75 mL), and washed with 1:1 water/saturated aqueous sodium thiosulfate (20 mL) and brine (20 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and dried under high vacuum at 95° C. to give (4S,7R)-2-(5-fluoro-2-trifluoromethyl-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (127 mg, 31%) as a white solid. ES(+)-MS (M+H) 369.

Workup

  1. waitin an oil bath at 50° C. for 1 h
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 1 h
  4. temperatureto cool to room temperature
  5. additionSilica gel was added
  6. customthe solvent was evaporated
  7. customThe residue was purified
  8. washeluting with 50-100% ethyl acetate/hexanes
  9. customFractions homogeneous for the product were evaporated
  10. dissolutionthe residue was dissolved in dichloromethane (75 mL)
  11. washwashed with 1:1 water/saturated aqueous sodium thiosulfate (20 mL) and brine (20 mL)
  12. dry with materialThe solution was dried (magnesium sulfate)
  13. filtrationfiltered
  14. customevaporated
  15. customdried under high vacuum at 95° C.

Sources & evidence

ORD record
ord-252549190c724846ba52698acd423ef9
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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