Hydrochloric Acid → HCID 57941422, compound

HRID 1438081Notes

Reaction equation

HRID 1438081 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]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=O)(C)(C)C.Cl.O1CCOCC1>ClCCCl.ClCCl>[C:32]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=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 57941381HCID 57941381, compound

Product 1

HCID 57941422HCID 57941422, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (1.7 mL, 12.2 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; 1.25 g, 5.82 mmol) in 1,2-dichloroethane (10 mL) over 1 min. A solution of N′-biphenyl-2-yl-N-methyl-hydrazinecarboxylic acid tert-butyl ester (1.09 g, 3.65 mmol) in 1,2-dichloroethane (15 mL) was added over 2 min. 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; 20 mL, 80 mmol) was added and the mixture was heated in an oil bath at 100° C. for 1.5 h. The reaction mixture was allowed to cool. Dichloromethane (200 mL) was added and the mixture was washed with 1:1 water/brine (50 mL), dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO 120 g column, eluting with 5-10% methanol/dichloromethane. Fractions homogeneous for the product were evaporated, and then co-evaporated successively with methanol, diethyl ether and then petroleum ether. The residue was treated with petroleum ether and the mixture was stirred for 20 min. The solid was filtered off and dried under high vacuum at 90° C. for 1 h to give (4S,7R)-2-biphenyl-2-yl-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (612 mg, 47%) as a light yellow solid. APCI(+)-MS (M+H) 359.

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 100° C. for 1.5 h
  4. temperatureto cool
  5. washthe mixture was washed with 1:1 water/brine (50 mL)
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. custompurified
  10. washeluting with 5-10% methanol/dichloromethane
  11. customFractions homogeneous for the product were evaporated
  12. additionThe residue was treated with petroleum ether
  13. stirringthe mixture was stirred for 20 min
  14. filtrationThe solid was filtered off
  15. customdried under high vacuum at 90° C. for 1 h

Sources & evidence

ORD record
ord-a14e2790ab87419e815630d2e6fd51f0
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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