2,6-Dimethylnicotinaldehyde → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol

HRID 526844Notes

Reaction equation

HRID 526844 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][C:32]1[N:39]=[C:38]([CH3:40])[CH:37]=[CH:36][C:33]=1[CH:34]=[O:35]>C1COCC1>[Cl:25][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([CH:34]([C:33]3[C:32]([CH3:31])=[N:39][C:38]([CH3:40])=[CH:37][CH:36]=3)[OH:35])[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

5

Reactant 3

HCID 27847532,6-DimethylnicotinaldehydeHCID 867156276-Bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline2×HCID 178418339Butyllithium

Product 1

HCID 86715629(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (1.85 g, 4.3 mmol, Intermediate 5: step d) was added THF (45 mL) at room temperature which resulted in a colorless homogeneous solution. The solution was cooled to −70° C. and then n-BuLi (2.5 M in hexanes, 1.75 mL, 4.38 mmol) was added dropwise. After 2 minutes, 2,6-dimethylnicotinaldehyde (755 mg, 5.50 mmol, in 2 mL THF) was introduced and the color of the mixture changed from a reddish-brown to green. The reaction mixture was allowed to warm to −20° C. over 40 minutes at which time the reaction was quenched with aqueous NH4Cl solution. The aqueous portion was extracted with EtOAc (3×50 mL) and the combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. Chromatography on silica gel (10% acetone-hexane increasing to 30% acetone) afforded the title compound.

Workup

  1. customresulted in a colorless homogeneous solution
  2. temperatureto warm to −20° C. over 40 minutes at which time the reaction
  3. customwas quenched with aqueous NH4Cl solution
  4. extractionThe aqueous portion was extracted with EtOAc (3×50 mL)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-269b1c36d3284c4b8e1e52fdd87d915e
Source dataset
uspto-grants-2016_05
Patent number
US09346782B2

Reaction notes

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