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

HRID 526848Notes

Reaction equation

HRID 526848 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)=[C:5]2[Cl:25].[Li]CCCC.[CH3:31][N:32]1[C:36]([CH:37]=[O:38])=[CH:35][N:34]=[CH:33]1.C(=O)=O>C1COCC1>[Cl:25][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([CH:37]([C:36]3[N:32]([CH3:31])[CH:33]=[N:34][CH:35]=3)[OH:38])[CH:3]=2)[N:8]=[C:7]([O:12][CH3:13])[C:6]=1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 5735921-methyl-1H-imidazole-5-carbaldehydeHCID 867156276-Bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline2×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 (3.0 g, 6.97 mmol, Intermediate 5: step d) 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 then 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. Chromatography on silica gel (30% acetone-DCM increasing to 5% MeOH) provided the title compound.

Workup

  1. additionwas then 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-ffe0434ae04247ccbbf787e9b61b120b
Source dataset
uspto-grants-2016_05
Patent number
US09346782B2

Reaction notes

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