Hydrochloric Acid → (4S,7R)-1-benzyl-7,8,8-trimethyl-2-naphthalen-2-yl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

HRID 1438077Notes

Reaction equation

HRID 1438077 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(OC([N:29]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[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>[CH2:41]([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)[C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=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 57941403N-benzyl-N'-naphthalen-2-yl-hydrazinecarboxylic acid tert-butyl ester2×

Product 1

HCID 57941405(4S,7R)-1-benzyl-7,8,8-trimethyl-2-naphthalen-2-yl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneYield 16%

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; 240 mg, 1.12 mmol) in 1,2-dichloroethane (8 mL) was added to a cooled (0° C.) solution of triethylamine (210 μL, 1.5 mmol) and N-benzyl-N′-naphthalen-2-yl-hydrazinecarboxylic acid tert-butyl ester (Intermediate 37; 285 mg, 0.82 mmol) in 1,2-dichloroethane (4 mL) over 1 min. The reaction mixture was stirred at room temperature for 75 min. A solution of HCl in dioxane (4 M; 4 mL, 16 mmol) was added and the reaction mixture was heated at reflux for 1 h, allowed to cool, and concentrated. The residue was purified using an ISCO 40 g column, eluting with 50-100% ethyl acetate/hexanes. Fractions containing the product were evaporated and purified again using an ISCO 40 g column, eluting with 60-100% ethyl acetate/hexanes. Fractions containing the product were evaporated, then co-evaporated with methanol and then with diethyl ether and dried under high vacuum at room temperature overnight to give (4S,7R)-1-benzyl-7,8,8-trimethyl-2-naphthalen-2-yl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (53 mg, 16%) as a white foam. ES(+)-MS (M+H) 409.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 1 h
  3. temperatureto cool
  4. concentrationconcentrated
  5. customThe residue was purified
  6. washeluting with 50-100% ethyl acetate/hexanes
  7. additionFractions containing the product
  8. customwere evaporated
  9. custompurified again
  10. washeluting with 60-100% ethyl acetate/hexanes
  11. additionFractions containing the product
  12. customwere evaporated
  13. dry with materialwith diethyl ether and dried under high vacuum at room temperature overnight

Sources & evidence

ORD record
ord-14b10b314b144d81b2edb8b317fdc0df
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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