Dimethylformamide → 1-Chloro-3-methyl-isoquinoline-4-carbaldehyde

HRID 606303Notes

Reaction equation

HRID 606303 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([Cl:12])=[N:4][C:3]=1[CH3:13].CN([CH:17]=[O:18])C>CCCCCC.C1COCC1>[Cl:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([CH:17]=[O:18])=[C:3]([CH3:13])[N:4]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 825722444-Bromo-1-chloro-3-methyl-isoquinoline

Product 1

HCID 866159291-Chloro-3-methyl-isoquinoline-4-carbaldehydeYield 81%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

n-BiLi (12.3 ml of 1.6 M in hexane, 20 mmol) is added dropwise to a solution of 4-bromo-1-chloro-3-methyl-isoquinoline (4.6 g, 18 mmol) in THF (80 ml) at −78° C. and the mixture is stirred for 40 min. DMF (4.2 ml, 54 mmol) is then added slowly. The cold bath is removed, and stirring is continued for 15 min. The mixture is acidified with 1N—HCl to pH 2 and extracted with ether. The combined extracts are dried over Na2SO4 and concentrated in vacuo. The residue is chromatographed on silica gel to give 3.0 g of 1-chloro-3-methyl-isoquinoline-4-carbaldehyde. 1H NMR (CDCl3) 10.9 (s, 1H), 9.06 (d, 1H), 8.40 (d, 1H), 7.88 (t, 1H), 7.70 (t, 1H), 2.99 (s, 3H).

Workup

  1. customThe cold bath is removed
  2. stirringstirring
  3. waitis continued for 15 min
  4. extractionextracted with ether
  5. dry with materialThe combined extracts are dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue is chromatographed on silica gel

Sources & evidence

ORD record
ord-f78d00767bec4bf2a2b72330d71cc318
Source dataset
uspto-grants-2011_03
Patent number
US07915288B2

Reaction notes

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