1,3-Dichloroisoquinoline → 3-Chloro-1-methylisoquinoline

HRID 2090060Notes

Reaction equation

HRID 2090060 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([Cl:12])[N:3]=1.[CH3:13][Al](C)C>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:12][C:4]1[N:3]=[C:2]([CH3:13])[C:11]2[C:6]([CH:5]=1)=[CH:7][CH:8]=[CH:9][CH:10]=2

Participants

5

Reactant 2

HCID 2986251,3-DichloroisoquinolineHCID 16682925Trimethylaluminum

Product 1

HCID 126941403-Chloro-1-methylisoquinoline

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1,3-dichloroisoquinoline (2.0 g, 10.1 mmol), trimethylaluminum (2.0 M in heptane, 6.1 mL, 12.1 mmol), and tetrakis(triphenylphosphine)palladium(0) (117 mg, 0.1 mmol) in THF (8 mL) was heated in a microwave reactor at 100° C. for 15 min. After quenching by addition of water (30 mL), the mixture was extracted with EtOAc. The organics were dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography eluting with 10% EtOAc/hexanes to afford the title compound: 1H NMR (500 MHz, CDCl3): δ 8.12 (dd, J=8.5, 0.5 Hz, 1H); 7.76 (d, J=8.0 Hz, 1H); 7.10 (dt, J=8.5, 0.5 Hz, 1H), 7.62-7.60 (m, 2H); 2.97 (s, 3H). LC6: 2.85 min, (M+H): 178.

Workup

  1. customAfter quenching by addition of water (30 mL)
  2. extractionthe mixture was extracted with EtOAc
  3. dry with materialThe organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 10% EtOAc/hexanes

Sources & evidence

ORD record
ord-33acf5ed1fbc42da854b868aa9b5e0a8
Source dataset
uspto-grants-2013_05
Patent number
US08436015B2

Reaction notes

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