Hydrochloric Acid → HCID 16116995, compound

HRID 1438044Notes

Reaction equation

HRID 1438044 reaction equation
C(N(CC)CC)C.C(O[C:13]([NH:15][N:16]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=1[F:25])C)=O)(C)(C)C.[CH3:26][C@:27]12[C:33]([CH3:35])([CH3:34])[C@H:30]([CH2:31][CH2:32]1)[CH:29]([C:36](Cl)=[O:37])[C:28]2=O.Cl.O1CCOCC1>ClCCCl>[Cl:24][C:20]1[C:19]([F:25])=[C:18]([N:16]2[C:36](=[O:37])[C:29]3[C@@H:30]4[C:33]([CH3:35])([CH3:34])[C@@:27]([CH3:26])([CH2:32][CH2:31]4)[C:28]=3[N:15]2[CH3:13])[CH:23]=[CH:22][CH:21]=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 69021397HCID 69021397, compound

Product 1

HCID 16116995HCID 16116995, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

Triethylamine (1 mL, 7.2 mmol) was added dropwise to a solution of N′-(3-chloro-2-fluoro-phenyl)-N′-methyl-hydrazinecarboxylic acid tert-butyl ester (434 mg, 1.6 mmol) in 1,2-dichloroethane (6 mL) over 1 min. The reaction mixture was stirred for 5 min and then a solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 800 mg, 3.7 mmol) in 1,2-dichloroethane (14 mL) was added over 2 min. The reaction mixture was heated in an oil bath at 50° C. for 1 h. The solution was allowed to cool and a solution of HCl in dioxane (4 M; 6 mL, 24 mmol) was added and the mixture was heated at reflux for 1.5 h and then allowed to cool to room temperature. The solvent was evaporated and the residue was purified on an ISCO system, eluting with 30-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and co-evaporated with methanol. The residue was triturated with ether/hexane and the solvent was removed with a pipet. The solid was drie under high vacuum at 90° C. to give (4S,7R)-2-(3-chloro-2-fluoro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (37 mg, 7%) as a white solid. ES(+)-MS (M+H) 335.

Workup

  1. temperatureto cool
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 1.5 h
  4. temperatureto cool to room temperature
  5. customThe solvent was evaporated
  6. customthe residue was purified on an ISCO system
  7. washeluting with 30-100% ethyl acetate/hexanes
  8. customFractions homogeneous for the product were evaporated
  9. customThe residue was triturated with ether/hexane
  10. customthe solvent was removed with a pipet
  11. customwas drie under high vacuum at 90° C.

Sources & evidence

ORD record
ord-256e7aab2ab34ce287e0cb68e965e7dc
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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