Water → CID 57941404

HRID 1437968Notes

Reaction equation

HRID 1437968 reaction equation
[CH3:1][C@@:2]12[C:22]([CH3:24])([CH3:23])[C@@H:5]([C:6]3[C:7](=[O:21])[N:8]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[C:17]([F:20])([F:19])[F:18])[NH:9][C:10]=31)[CH2:4][CH2:3]2.I[CH3:26].O>CN(C)C=O>[CH3:26][N:9]1[C:10]2[C@@:2]3([CH3:1])[C:22]([CH3:24])([CH3:23])[C@H:5]([CH2:4][CH2:3]3)[C:6]=2[C:7](=[O:21])[N:8]1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]([F:18])([F:19])[F:20]

Participants

5

Reactant 3

HCID 962WaterHCID 6328Methyl iodideHCID 57941458(4s,7r)-2-(2-Trifluoromethyl-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 1

HCID 57941404CID 57941404Yield 81.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4S,7R)-7,8,8-trimethyl-2-(2-trifluoromethyl-phenyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 22; 710 mg, 2.1 mmol) and iodomethane (0.33 mL, 5.3 mmol) in N,N-dimethylformamide (5 mL) in a sealed tube was heated at 100° C. overnight. Water was added and the reaction mixture was extracted three times with ethyl acetate. The combined organic extracts were washed with water and brine, dried (magnesium sulfate), filtered, evaporated, and purified using an Analogix Intelliflash 280 system (Analogix, Inc., Burlington, Wis.) with an Analytical Sales Aspire 90 g column, eluting with 25-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, dissolved in ethyl acetate and heated at reflux with activated charcoal for 10 min. The mixture was filtered through Celite® and evaporated to give (4S,7R)-1,7,8,8-tetramethyl-2-(2-trifluoromethyl-phenyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (602 mg, 81%) as a light yellow solid. ES(+)-MS (M+H) 351.

Workup

  1. extractionthe reaction mixture was extracted three times with ethyl acetate
  2. washThe combined organic extracts were washed with water and brine
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. custompurified
  7. washeluting with 25-100% ethyl acetate/hexanes
  8. customFractions homogeneous for the product were evaporated
  9. dissolutiondissolved in ethyl acetate
  10. temperatureheated
  11. temperatureat reflux with activated charcoal for 10 min
  12. filtrationThe mixture was filtered through Celite®
  13. customevaporated

Sources & evidence

ORD record
ord-d96e451984ac483e8c851757c05d20bd
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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