Dimethylformamide → 1-Chloroisoquinoline-5-carbaldehyde

HRID 1067235Notes

Reaction equation

HRID 1067235 reaction equation
[Li]CCCC.Br[C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[CH:9]=[CH:10][N:11]=[C:12]2[Cl:17].CN([CH:21]=[O:22])C>>[Cl:17][C:12]1[C:13]2[CH:14]=[CH:15][CH:16]=[C:7]([CH:21]=[O:22])[C:8]=2[CH:9]=[CH:10][N:11]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 211924975-Bromo-1-chloroisoquinolineHCID 178418339Butyllithium

Product 1

HCID 211924671-Chloroisoquinoline-5-carbaldehydeYield 39.1%

Procedure

A solution of n-BuLi (1.76 mL, 2.5 M in hexanes, 4.4 mmol) was added to a stirred solution of 5-bromo-1-chloroisoquinoline (Braye, E.; Eloy, F.; Hoogzand, C.; Lenaers, R. Eur. J. Med. Chem., Chim. Therap. 1974, 9, 197) (1.0 g, 4.12 mmol) in THF-ether (36 mL, 1:1) at −78° C. under N2. After 20 minutes, DMF (0.66 mL, 8.5 mmol) was added and after an additional 30 minutes at −78° C. the reaction was quenched with EtOH (3 mL) and warmed to room temperature. The mixture was diluted with ether (150 mL), washed with saturated NH4Cl (50 mL), brine, dried over MgSO4, and evaporated in vacuo. The residue was purified by column chromatography upon silica gel using hexanes-EtOAc (95:5 to 50:50) as eluant to give 1-chloro-5-isoquinolinecarboxaldehyde (308 mg, 1.61 mmol) as a white solid.

Workup

  1. customwas quenched with EtOH (3 mL)
  2. additionThe mixture was diluted with ether (150 mL)
  3. washwashed with saturated NH4Cl (50 mL), brine
  4. dry with materialdried over MgSO4
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography upon silica gel

Sources & evidence

ORD record
ord-2db20f70312c4b0faae77f834086eea9
Source dataset
uspto-grants-2001_06
Patent number
US06248738B1

Reaction notes

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