Carbon Dioxide → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 926561Notes

Reaction equation

HRID 926561 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([C:14]3C(C)=NC(C)=C[CH:19]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([O:22][CH3:23])[C:3]=1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=1.[Li]CCCC.[CH3:40][N:41]1C(C=O)=C[N:43]=[CH:42]1.C(=O)=O>C1COCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([C:14]3[N:41]([CH3:40])[CH:42]=[N:43][CH:19]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([O:22][CH3:23])[C:3]=1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:32])([F:33])[F:34])=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 5735921-methyl-1H-imidazole-5-carbaldehydeHCID 86715629(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol2×HCID 178418339Butyllithium

Product 1

HCID 118006081(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (Intermediate 12: step d, 3.0 g, 6.97 mmol) was added THF (40 ml) and the solution was cooled to −70° C. n-BuLi (2.5 M in hexanes, 2.8 mL, 7 mmol) was added dropwise. After 2 minutes, 1-methyl-1H-imidazole-5-carbaldehyde (1.2 g, 9 mmol, in 10 mL THF) was introduced. After 15 minutes, the dry-ice bath was replaced with a 0° C. bath. After 35 minutes the reaction mixture was quenched with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc:THF (10:2) 5×50 mL. The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated to dryness to give the title compound.

Workup

  1. additionwas added dropwise
  2. waitAfter 15 minutes
  3. customwas replaced with a 0° C.
  4. customAfter 35 minutes the reaction mixture was quenched with aqueous NH4Cl solution
  5. extractionthe aqueous portion was extracted with EtOAc:THF (10:2) 5×50 mL
  6. washThe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-d70b1799145744728bfb09863fd09c0d
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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