Picolinic acid → HCID 16118896, compound

HRID 1437916Notes

Reaction equation

HRID 1437916 reaction equation
[CH3:1][N:2]1[C:10]2[C@@:9]3([CH3:14])[C:11]([CH3:13])([CH3:12])[C@H:6]([CH2:7][CH2:8]3)[C:5]=2[C:4](=[O:15])[NH:3]1.[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1I.N1C=CC=CC=1C(O)=O.C(=O)(O)[O-].[K+]>CN(C)C=O.Cl.C(OCC)(=O)C.[Cu]I>[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:3]1[C:4](=[O:15])[C:5]2[C@@H:6]3[C:11]([CH3:12])([CH3:13])[C@@:9]([CH3:14])([CH2:8][CH2:7]3)[C:10]=2[N:2]1[CH3:1]

Participants

9

Reactant 4

HCID 1018Picolinic acidHCID 119931-Chloro-2-iodobenzeneHCID 516893Potassium BicarbonateHCID 57941341HCID 57941341, compound2×

Product 1

HCID 16118896HCID 16118896, compoundYield 5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (4S,7R)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 19; 1.24 g, 6 mmol), 1-chloro-2-iodobenzene (666 μL, 5.4 mmol), copper(I) iodide (57 mg, 0.3 mmol), picolinic acid (150 mg, 1.2 mmol), and potassium bicarbonate (840 mg, 8.4 mmol) in N,N-dimethylformamide (20 mL) was irradiated in a microwave oven at 200° C. for 160 min. The reaction mixture was diluted with 0.1 M HCl (200 mL) and then extracted with ethyl acetate (200 mL). The organic layer was washed with 0.1 M HCl, 0.25 M NaOH, and brine, then dried (magnesium sulfate), filtered, evaporated and purified using an ISCO CombiFlash® Sg100c chromatography system, eluting with 5-100% ethyl acetate/dichloromethane to give a tan semi-solid which was taken up in ethyl acetate and washed with 0.1 M HCR. The solvent was evaporated and the residue was recrystallized from ethyl acetate. The mother liquor was evaporated and the residue recrystallized from ethyl acetate. The crystals were combined to give (4S,7R)-2-(2-chloro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (80 mg, 5%) as a white solid. APCI-MS (M+H) 317.

Workup

  1. customwas irradiated in a microwave oven at 200° C. for 160 min
  2. extractionextracted with ethyl acetate (200 mL)
  3. washThe organic layer was washed with 0.1 M HCl, 0.25 M NaOH, and brine
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified
  8. washeluting with 5-100% ethyl acetate/dichloromethane
  9. customto give a tan semi-solid which
  10. washwashed with 0.1 M HCR
  11. customThe solvent was evaporated
  12. customthe residue was recrystallized from ethyl acetate
  13. customThe mother liquor was evaporated
  14. customthe residue recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-aa503e4c23fd4493b3c902372a43fd4e
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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