Acetic Acid → 3,4-Dimethoxy-6-(2-bromoisonicotinoyl)benzaldehyde dimethyl acetal

HRID 1739422Notes

Reaction equation

HRID 1739422 reaction equation
[CH3:1][O:2][CH:3]([O:15][CH3:16])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=1Br.C([Li])CCC.[Br:22][C:23]1[CH:24]=[C:25]([CH:31]=[CH:32][N:33]=1)[C:26](N(C)C)=[O:27].C(O)(=O)C>O1CCCC1.O>[CH3:1][O:2][CH:3]([O:15][CH3:16])[C:4]1[C:5]([C:26](=[O:27])[C:25]2[CH:31]=[CH:32][N:33]=[C:23]([Br:22])[CH:24]=2)=[CH:6][C:7]([O:12][CH3:13])=[C:8]([O:10][CH3:11])[CH:9]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 27625002-Bromo-N,N-dimethylisonicotinamideHCID 110771461-Bromo-2-(dimethoxymethyl)-4,5-dimethoxybenzeneHCID 178418339Butyllithium

Product 1

HCID 218408043,4-Dimethoxy-6-(2-bromoisonicotinoyl)benzaldehyde dimethyl acetalYield 46.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-bromo-4,5-dimethoxybenzaldehyde dimethyl acetal (21.8 g) in tetrahydrofuran (80 ml) is added dropwise a solution of n-butyl lithium (1.6 M hexane solution, 46.8 ml) at a temperature below -50° C. under nitrogen atmosphere, and the mixture is stirred for 20 minutes. The resulting solution is added dropwise into a solution of 2-bromo-N,N-dimethylisonicotinamide (18.1 g) in tetrahydrofuran (80 ml) at a temperature below -60° C., and the mixture is stirred for 30 minutes. To the reaction mixture is added acetic acid (4.5 ml), and the mixture is poured into water, and extracted with ethyl acetate. The extract is washed, dried, and concentrated, and the residue is purified by silica gel column chromatography (solvent; hexane:ethyl acetate=2:1) to give 3,4-dimethoxy-6-(2-bromoisonicotinoyl)benzaldehyde dimethyl acetal (13.9 g) as an oily product.

Workup

  1. stirringthe mixture is stirred for 30 minutes
  2. extractionextracted with ethyl acetate
  3. washThe extract is washed
  4. customdried
  5. concentrationconcentrated
  6. customthe residue is purified by silica gel column chromatography (solvent; hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-7e07426a0d5749e887f8cfd941d8c1ef
Source dataset
uspto-grants-1999_10
Patent number
US05965730

Reaction notes

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