Sodium Hydroxide → 1-Chloro-3-ethoxyisoquinoline

HRID 2405781Notes

Reaction equation

HRID 2405781 reaction equation
[CH2:1]([O:3][C:4]1[N+:5]([O-])=[CH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH3:2].[OH-].[Na+].O=P(Cl)(Cl)[Cl:19]>C(Cl)(Cl)Cl>[Cl:19][C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:13]=[C:4]([O:3][CH2:1][CH3:2])[N:5]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 686175523-ethoxyisoquinoline N-oxide

Product 1

HCID 574451481-Chloro-3-ethoxyisoquinolineYield 40%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
120 °C

Procedure

3-Ethoxyisoquinoline N-oxide (1.15 g, 6.1 mmol) was taken up in POCl3 (5 mL) at rt and then heated to 120° C. under an atmosphere of Ar for 2 h. Following cooling to it, the reaction was diluted with CHCl3 and poured into icewater (20 mL) and the resulting solution was placed in an ice bath and treated with 10M NaOH until pH 10 with vigorous stirring. Following extraction with CHCl3, the combined organics were washed with brine and dried over anhydrous MgSO4. Following concentration in vacuo, purification on SiO2 (3-15% EtOAc/hex) afforded 0.51 g (40%) of 1-chloro-3-ethoxyisoquinoline. LCMS found 208.1 [M+H]+.

Workup

  1. temperatureFollowing cooling to it
  2. additionpoured into icewater (20 mL)
  3. customthe resulting solution was placed in an ice bath
  4. extractionextraction with CHCl3
  5. washthe combined organics were washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentration
  8. customin vacuo, purification on SiO2 (3-15% EtOAc/hex)

Sources & evidence

ORD record
ord-9993585a9bd84d6e9d345cc39d0c2d35
Source dataset
uspto-grants-2014_08
Patent number
US08809267B2

Reaction notes

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