Water → 7-Chloro-3-methylisoquinoline

HRID 1432853Notes

Reaction equation

HRID 1432853 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=2)[CH:5]=[C:4]([CH3:13])[N:3]=1.O.C(Cl)Cl.[OH-].[Na+]>C(O)(=O)C.CCOC(C)=O.[Zn]>[Cl:12][C:9]1[CH:10]=[C:11]2[C:6]([CH:5]=[C:4]([CH3:13])[N:3]=[CH:2]2)=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 213880331,7-Dichloro-3-methylisoquinoline

Product 1

HCID 206167957-Chloro-3-methylisoquinoline

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1,7-dichloro-3-methyl-isoquinoline (0.50 g, 2.36 mmol), Example 10, part C, in 5.5 mL of 9:1 acetic acid:H2O at 75° C. is added zinc (0.23 g, 3.54 mmol) After 75 minutes, the solution is cooled to ambient temperatures. The solution is diluted with a 4:1 EtOAc:CH2Cl2 solution. To the solution is added 100 mL of a 1N NaOH solution. The aqueous solution is extracted with 4:1 EtOAc:CH2Cl2. The combined organic layers are washed with a saturated NaCl solution. The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with a gradient of 5% EtOAc/hexanes to 15% EtOAc/hexanes. The title compound is obtained as a white solid (0.36 g, 1.97 mmol). 1H NMR (CDCl3, 300 MHz) δ9.09 (s, 1H), 7.89 (s, 1H), 7.61 (d, 1H), 7.55 (d, 1H), 7.44 (s, 1H) 2.68 (s, 3H). MS (EI): m/z 177, 179 (M+), Cl pattern.

Workup

  1. temperaturethe solution is cooled to ambient temperatures
  2. extractionThe aqueous solution is extracted with 4:1 EtOAc
  3. washThe combined organic layers are washed with a saturated NaCl solution
  4. dry with materialThe organic layer is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by column chromatography
  8. washeluting with a gradient of 5% EtOAc/hexanes to 15% EtOAc/hexanes

Sources & evidence

ORD record
ord-595e036b8b124e528a56eb6c6c912ffc
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

Loading…