Picolinic acid → HCID 57941482, compound

HRID 1437932Notes

Reaction equation

HRID 1437932 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.I[C:17]1[CH:18]=[C:19]([O:23][CH3:24])[CH:20]=[CH:21][CH:22]=1.N1C=CC=CC=1C(O)=O.C(=O)(O)[O-].[K+]>CN(C)C=O.Cl.C(OCC)(=O)C.[Cu]I>[CH3:24][O:23][C:19]1[CH:18]=[C:17]([N:3]2[C:4](=[O:15])[C:5]3[C@@H:6]4[C:11]([CH3:12])([CH3:13])[C@@:9]([CH3:14])([CH2:8][CH2:7]4)[C:10]=3[N:2]2[CH3:1])[CH:22]=[CH:21][CH:20]=1

Participants

9

Reactant 4

HCID 1018Picolinic acidHCID 69839Benzene, 1-iodo-3-methoxy-HCID 516893Potassium BicarbonateHCID 57941341HCID 57941341, compound2×

Product 1

HCID 57941482HCID 57941482, compoundYield 20%

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; 412 mg, 2 mmol), 3-iodo-methoxy-benzene (264 μL, 2.2 mmol), copper(I) iodide (19 mg, 0.1 mmol), picolinic acid (49 mg, 0.4 mmol), and potassium bicarbonate (280 mg, 2.8 mmol) in N,N-dimethylformamide (10 mL) was irradiated in a microwave oven at 220° C. for 30 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 system, eluting with 5-60% ethyl acetate/dichloromethane to give a tan semi-solid. This was dissolved in ethyl acetate (30 mL) and washed with 0.1 M HCl (30 mL), then dried, filtered, evaporated and triturated with petroleum ether to give (4S,7R)-2-(3-methoxy-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (107 mg, 20%) as a white solid. ES(+)-MS (M+H) 313.

Workup

  1. customwas irradiated in a microwave oven at 220° C. for 30 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 5-60% ethyl acetate/dichloromethane
  9. customto give a tan semi-solid
  10. washwashed with 0.1 M HCl (30 mL)
  11. customdried
  12. filtrationfiltered
  13. customevaporated
  14. customtriturated with petroleum ether

Sources & evidence

ORD record
ord-b5fadbec9c0945408f428409467e3a89
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

Loading…