Hydrochloric Acid → HCID 57941496, compound

HRID 1438048Notes

Reaction equation

HRID 1438048 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]([NH:29][N:30]([C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][C:33]=1[Cl:39])C)=O)(C)(C)C.Cl.O1CCOCC1>ClCCCl.ClCCl>[Cl:39][C:33]1[CH:34]=[C:35]([Cl:38])[CH:36]=[CH:37][C:32]=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

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 69019367HCID 69019367, compound

Product 1

HCID 57941496HCID 57941496, compoundYield 46.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Triethylamine (450 μL, 3.2 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; 361 mg, 1.68 mmol) in 1,2-dichloroethane (3 mL) over 1 min. The reaction mixture was stirred for 5 min and then a solution of N′-(2,4-dichloro-phenyl)-N′-methyl-hydrazinecarboxylic acid tert-butyl ester (310 mg, 1.07 mmol) in 1,2-dichloroethane (6 mL) was added over 2 min. The reaction mixture was stirred at 0° C. for 15 min, at room temperature for 30 min, and then in an oil bath at 50° C. for 2 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 and then allowed to cool to room temperature. Dichloromethane (100 mL) was added and the mixture was washed with 1:1 water/brine (20 mL), dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO 40 g column, eluting with 20-50% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and co-evaporated successively with methanol, diethyl ether and petroleum ether. The residue was triturated with hexanes, and the solid was dried overnight under high vacuum at 70° C. and then at 85° C. for 1 h to give (4S,7R)-2-(2,4-dichloro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (175 mg, 45%) as an off-white solid. ES(+)-MS (M+H) 351.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 15 min, at room temperature for 30 min
  2. waitin an oil bath at 50° C. for 2 h
  3. temperatureto cool to room temperature
  4. washthe mixture was washed with 1:1 water/brine (20 mL)
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. customevaporated
  8. custompurified
  9. washeluting with 20-50% ethyl acetate/hexanes
  10. customFractions homogeneous for the product were evaporated
  11. customThe residue was triturated with hexanes
  12. customthe solid was dried overnight under high vacuum at 70° C.

Sources & evidence

ORD record
ord-94c8a694bcdf415db45ab0ddf86bb3c8
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

Loading…