Carbon Dioxide → HCID 86715656, compound

HRID 928825Notes

Reaction equation

HRID 928825 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 to a stirred solution of 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (1.01 g, 2.35 mmol, Intermediate 47, step d) in THF (11.5 mL) under argon at ˜−70° C. After an additional 1 min, 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 min, the resulting homogeneous yellow reaction was removed from the cold bath and stirred under ambient conditions for 5 min, 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 min, and was then rotovapped at rt 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 min. The resulting opaque thin slurry was then diluted with DCM (15 mL), washed with water (2×25 mL), dried (Na2SO4), filtered, and concentrated to provide a white solid. This 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 min, 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 min
  8. customwas then rotovapped at rt
  9. customto provide a thick light yellow slurry
  10. stirringstirred at 40° C. for 30 min
  11. washwashed with water (2×25 mL)
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto provide a white solid
  16. customThis was recrystallized from hot heptane (10 mL)
  17. filtrationthe globular crystals were filtered
  18. washwashed with heptane (2×6 mL)

Sources & evidence

ORD record
ord-4488010a036a41d5bb9b0ff363dd6505
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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