Dimethylformamide → 3-(5-(Trifluoromethyl)pyridin-2-yloxy)benzaldehyde

HRID 1666485Notes

Reaction equation

HRID 1666485 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][N:7]=1.CN([CH:22]=[O:23])C.[Li]CCCC>C1COCC1>[F:13][C:12]([F:15])([F:14])[C:9]1[CH:10]=[CH:11][C:6]([O:5][C:4]2[CH:3]=[C:2]([CH:18]=[CH:17][CH:16]=2)[CH:22]=[O:23])=[N:7][CH:8]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 8945092-(3-Bromophenoxy)-5-(trifluoromethyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 866239163-(5-(Trifluoromethyl)pyridin-2-yloxy)benzaldehydeYield 23.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(3-bromophenoxy)-5-(trifluoromethyl)pyridine (8.0 g, 25.15 mmol) in THF under inert atmosphere at −78° C. was added DMF (3.8 mL, 50.3 mmol) dropwise, followed by n-BuLi (31.4 mL, 50.3 mmol) dropwise. The reaction mixture was stirred for 1 h. The reaction mixture was quenched with saturated NH4Cl solution and the temperature was allowed to warm to room temperature. The mixture was extracted with ethyl acetate, dried over Na2SO4, and concentrated to dryness. Purification by column chromatography (EtOAc:Hexane, 40:60) gave the pure title compound (1.6 g). 1H NMR (500 MHz, CDCl3): δ 7.1 (d, 1H, J=8.5 Hz), 7.4 (m, 1H), 7.6 (m, 1H), 7.7 (d, 1H, J=7.5 Hz), 7.9 (1H), 8.4 (s, 1H), 10.0 (s, 1H).

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl solution
  2. extractionThe mixture was extracted with ethyl acetate
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to dryness
  5. customPurification by column chromatography (EtOAc:Hexane, 40:60)

Sources & evidence

ORD record
ord-37182f779466406da7ad02a6bf7ea23d
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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