Hydrochloric Acid → HCID 57941353, compound

HRID 1438074Notes

Reaction equation

HRID 1438074 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:40]=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=1)=O)(C)(C)C.Cl.O1CCOCC1>ClCCCl>[CH3:27][N:29]1[C:3]2[C@:2]3([CH3:1])[C:8]([CH3:10])([CH3:9])[C@@H:5]([CH2:6][CH2:7]3)[C:4]=2[C:11](=[O:12])[N:30]1[C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 57941318HCID 57941318, compound2×HCID 57941380HCID 57941380, compound2×

Product 1

HCID 57941353HCID 57941353, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

A solution of (1S,4S)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 25; 530 mg, 2.47 mmol) in 1,2-dichloroethane (12 mL) was added to a cooled (0° C.) solution of triethylamine (470 μL, 3.37 mmol) and N-methyl-N′-naphthalen-2-yl-hydrazinecarboxylic acid tert-butyl ester (Intermediate 36; 450 mg, 1.65 mmol) in 1,2-dichloroethane (6 mL) over 1 min. The reaction mixture was stirred at room temperature for 90 min. A solution of HCl in dioxane (4 M; 10 mL, 40 mmol) was added and the reaction mixture was heated at reflux for 90 min, and allowed to cool. The solvent was evaporated. The residue was purified twice using ISCO 40 g columns. The first column was eluted with 50-100% ethyl acetate and then with 10% methanol/ethyl acetate. The second column was eluted with 60-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated and the residue was co-evaporated with methanol and then with diethyl ether, and dried under high vacuum at room temperature to give (4R,7S)-1,7,8,8-tetramethyl-2-naphthalen-2-yl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (170 mg, 31%) as an off-white foam. ES(+)-MS (M+H) 333.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 90 min
  3. temperatureto cool
  4. customThe solvent was evaporated
  5. customThe residue was purified twice using ISCO 40 g columns
  6. washThe first column was eluted with 50-100% ethyl acetate
  7. washThe second column was eluted with 60-100% ethyl acetate/hexanes
  8. customFractions homogeneous for the product were evaporated
  9. dry with materialwith diethyl ether, and dried under high vacuum at room temperature

Sources & evidence

ORD record
ord-ba3308926c1746b195ed2e2461885712
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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