Hydrochloric Acid → HCID 57941488, compound

HRID 1438070Notes

Reaction equation

HRID 1438070 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:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[CH:33][C:32]=1[C:41]([F:44])([F:43])[F:42])=O)(C)(C)C.Cl.O1CCOCC1.O.[Cl-].[Na+].O>ClCCCl.ClCCl>[F:42][C:41]([F:43])([F:44])[C:32]1[CH:33]=[CH:34][C:35]([C:37]([F:40])([F:39])[F:38])=[CH:36][C:31]=1[N:30]1[C:11](=[O:12])[C:4]2[C@@H:5]3[C:8]([CH3:10])([CH3:9])[C@@:2]([CH3:1])([CH2:7][CH2:6]3)[C:3]=2[N:29]1[CH3:27]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 23713072Sodium chloride dihydrateHCID 57941306(1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride2×HCID 57941520HCID 57941520, compound

Product 1

HCID 57941488HCID 57941488, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 415 mg, 1.93 mmol) in 1,2-dichloroethane (12 mL) was added to a cooled (0° C.) solution of triethylamine (380 μL, 2.73 mmol) and N′-(2,5-bis-trifluoromethyl-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (480 mg, 1.34 mmol) in 1,2-dichloroethane (8 mL) over a period of 1 min. The reaction mixture was stirred for 10 min at room temperature and then in an oil bath at 50° C. for 45 min. A solution of HCl in dioxane (4 M; 10 mL, 40 mmol) was added and the mixture was heated at reflux for 1.5 h and then allowed to cool to room temperature. Dichloromethane (75 mL) and 1:1 water/brine (20 mL) were added. The mixture was shaken and the layers separated. The aqueous layer was back-extracted with dichloromethane (30 mL). The combined organic layers were dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO40 g column, eluting with 40-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, co-evaporated successively with methanol and ether, and then dried under high vacuum at 95° C. to give (4S,7R)-2-(2,5-bis-trifluoromethyl-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (256 mg, 46%) as an off-white solid. ES(+)-MS (M+H) 419.

Workup

  1. waitin an oil bath at 50° C. for 45 min
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 1.5 h
  4. temperatureto cool to room temperature
  5. stirringThe mixture was shaken
  6. customthe layers separated
  7. extractionThe aqueous layer was back-extracted with dichloromethane (30 mL)
  8. dry with materialThe combined organic layers were dried (magnesium sulfate)
  9. filtrationfiltered
  10. customevaporated
  11. custompurified
  12. washeluting with 40-100% ethyl acetate/hexanes
  13. customFractions homogeneous for the product were evaporated, co-evaporated successively with methanol and ether
  14. customdried under high vacuum at 95° C.

Sources & evidence

ORD record
ord-8fe5849740d348eabb1dc9bd3bac8485
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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