Hydrochloric Acid → HCID 57941406, compound

HRID 1437986Notes

Reaction equation

HRID 1437986 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]=[CH:35][CH:34]=[CH:33][C:32]=1[C:37]#[N:38])=O)(C)(C)C.Cl.O1CCOCC1>ClCCCl.ClCCl>[CH3:27][N:29]1[C:10]2[C@@:9]3([CH3:8])[C:15]([CH3:17])([CH3:16])[C@H:12]([CH2:13][CH2:14]3)[C:11]=2[C:18](=[O:19])[N:30]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[C:37]#[N:38]

Participants

8

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 57941326HCID 57941326, compound

Product 1

HCID 57941406HCID 57941406, compoundYield 10.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (0.82 mL, 5.9 mmol) was added dropwise to a cooled (0° C.) solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 690 mg, 3.21 mmol) in 1,2-dichloroethane (6 mL) over 1 min. A solution of N′-(2-cyano-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (435 mg, 1.76 mmol) in 1,2-dichloroethane (10 mL) was added. The reaction mixture was stirred at 0° C. for 15 min, at room temperature for 15 min, and then in an oil bath at 50° C. for 1 h. The reaction mixture was cooled. A solution of HCl in dioxane (4 M; 6 mL, 24 mmol) was added and the mixture was heated in an oil bath at 50° C. for 30 min and then at 100° C. for 1 h and allowed to cool. Dichloromethane (150 mL) was added and the mixture was washed with 1:1 water/brine (30 mL), dried (magnesium sulfate), filtered, evaporated, and purified by flash chromatography, eluting with 50-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and then co-evaporated with methanol and then diethyl ether. The residue was dried under high vacuum at 70° C. to give 2-((4S,7R)-1,7,8,8-tetramethyl-3-oxo-1,3,4,5,6,7-hexahydro-4,7-methano-indazol-2-yl)-benzonitrile (55 mg, 10%) as an off-white solid. ES(+)-MS (M+H) 308.

Workup

  1. waitin an oil bath at 50° C. for 1 h
  2. temperatureThe reaction mixture was cooled
  3. temperaturethe mixture was heated in an oil bath at 50° C. for 30 min
  4. waitat 100° C. for 1 h
  5. temperatureto cool
  6. washthe mixture was washed with 1:1 water/brine (30 mL)
  7. dry with materialdried (magnesium sulfate)
  8. filtrationfiltered
  9. customevaporated
  10. custompurified by flash chromatography
  11. washeluting with 50-100% ethyl acetate/hexanes
  12. customFractions homogeneous for the product were evaporated
  13. customThe residue was dried under high vacuum at 70° C.

Sources & evidence

ORD record
ord-e22ce0c4b8f94e83930c76f19f78ddbd
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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