Carbon Dioxide → HCID 86715656, compound

HRID 926557Notes

Reaction equation

HRID 926557 reaction equation
[Li]CCCC.[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH:17](C3C(C)=NC(C)=CC=3)[OH:18])[CH:15]=2)[N:10]=[C:9]([O:27][CH3:28])[C:8]=1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=1.[C:40](=O)=[O:41].IC>C1COCC1.C(Cl)Cl.CS(C)=O>[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]([O:41][CH3:40])=[O:18])[CH:15]=2)[N:10]=[C:9]([O:27][CH3:28])[C:8]=1[CH2:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]([F:38])([F:39])[F:37])=[CH:34][CH:35]=1

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 6328Methyl iodide2×HCID 86715629(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol2×HCID 178418339Butyllithium

Product 1

HCID 86715656HCID 86715656, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

n-BuLi (2.66 M in hexanes, 0.883 mL, 2.35 mmol) was added dropwise over 4 minutes to a stirred solution of 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (1.01 g, 2.35 mmol, Intermediate 12: step d) in THF (11.5 mL) under argon at ˜−70° C. After an additional minute, a pellet of dry ice (˜4 g, ˜90 mmol) was added to the dark solution, and the flask was quickly resealed, evacuated and flushed with argon. After another minute, the resulting homogeneous yellow reaction was removed from the cold bath and stirred under ambient conditions for 5 minutes, and was then transferred to an ice bath and quenched with iodomethane (0.146 mL, 2.35 mmol) and DMSO (4.6 mL). The clear yellow reaction was stirred at 0° C. for 5 minutes, and was then concentrated to remove the THF at room temperature to provide a thick light yellow slurry. This was treated with Li2CO3 (173 mg, 2.35 mmol) and iodomethane (0.438 mL, 7.03 mmol) and stirred at 40° C. for 30 minutes. The resulting opaque thin slurry was then diluted with DCM (15 mL), washed with water (2×25 mL), dried (Na2SO4), filtered, and concentrated to dryness to provide a white solid. This solid was recrystallized from hot heptane (10 mL), and the globular crystals were filtered and washed with heptane (2×6 mL) to provide the title compound as an off-white powder.

Workup

  1. customevacuated
  2. customflushed with argon
  3. customAfter another minute, the resulting homogeneous yellow reaction
  4. customwas removed from the cold bath
  5. customwas then transferred to an ice bath
  6. customThe clear yellow reaction
  7. stirringwas stirred at 0° C. for 5 minutes
  8. concentrationwas then concentrated
  9. customto remove the THF at room temperature
  10. customto provide a thick light yellow slurry
  11. stirringstirred at 40° C. for 30 minutes
  12. washwashed with water (2×25 mL)
  13. dry with materialdried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated to dryness
  16. customto provide a white solid
  17. customThis solid was recrystallized from hot heptane (10 mL)
  18. filtrationthe globular crystals were filtered
  19. washwashed with heptane (2×6 mL)

Sources & evidence

ORD record
ord-8ec4ff616fa349b3b80f9e826319f34a
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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