Hydrochloric Acid → HCID 16116997, compound

HRID 1438050Notes

Reaction equation

HRID 1438050 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]=[C:35]([Cl:37])[CH:34]=[CH:33][C:32]=1[Cl:38])=O)(C)(C)C.Cl.O1CCOCC1>ClCCCl>[Cl:38][C:32]1[CH:33]=[CH:34][C:35]([Cl:37])=[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

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 57941380HCID 57941380, compound2×HCID 57941390HCID 57941390, compound2×

Product 1

HCID 16116997HCID 16116997, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent3×

Procedure

Triethylamine (440 μL, 3.2 mmol) was added to solution of (1S,4S)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 25; 329 mg, 1.5 mmol) in 1,2-dichloroethane (4 mL) over 1 min. Then a solution of N′-(2,5-dichloro-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (300 mg, 1.03 mmol) in 1,2-dichloroethane (8 mL) was added over 2 min. The reaction mixture was stirred at room temperature for 15 min and then heated in an oil bath at 50° C. for 30 min. An additional portion of N′-(2,5-dichloro-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (290 mg, 1.0 mmol) in 1,2-dichloroethane (4 mL) was added and the mixture was heated in an oil bath at 50° C. for 1.5 h. 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. The reaction mixture was allowed to cool, silica gel was added, the solvent was evaporated and the mixture was purified using an ISCO 40 g column, eluting with 60-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, co-evaporated successively with methanol and diethyl ether, and then dried under high vacuum at 95° C. to give (4R,7S)-2-(2,5-dichloro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (24 mg, 37%) as a pale yellow solid. ES(+)-MS (M+H) 351.

Workup

  1. temperatureheated in an oil bath at 50° C. for 30 min
  2. temperaturethe mixture was heated in an oil bath at 50° C. for 1.5 h
  3. temperaturethe mixture was heated in an oil-bath at 100° C. for 1 h
  4. temperatureto cool
  5. additionsilica gel was added
  6. customthe solvent was evaporated
  7. customthe mixture was purified
  8. washeluting with 60-100% ethyl acetate/hexanes
  9. customFractions homogeneous for the product were evaporated, co-evaporated successively with methanol and diethyl ether
  10. customdried under high vacuum at 95° C.

Sources & evidence

ORD record
ord-0ce2ee1fc9ef4387a26ee23117f53062
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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