3,5-Dimethoxyisonicotinaldehyde → 3-Hydroxy-5-methoxyisonicotinaldehyde

HRID 1471737Notes

Reaction equation

HRID 1471737 reaction equation
C[O:2][C:3]1[CH:10]=[N:9][CH:8]=[C:7]([O:11][CH3:12])[C:4]=1[CH:5]=[O:6].[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)Cl>[OH:2][C:3]1[CH:10]=[N:9][CH:8]=[C:7]([O:11][CH3:12])[C:4]=1[CH:5]=[O:6]

Participants

4

Reactant 2

HCID 27629823,5-DimethoxyisonicotinaldehydeHCID 6451240Aluminum(III) Chloride

Product 1

HCID 722180533-Hydroxy-5-methoxyisonicotinaldehydeYield 17%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3,5-dimethoxyisonicotinaldehyde (2.7 g, 16.16 mmol, 1 eq.) in DCM (100 mL) was added AlCl3 (4.31 g, 32.32 mmol, 2.0 eq.) at rt. The mixture was reflux O/N, cooled to rt, and added into ice (200 g). The aqueous layer was extracted with DCM three times. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 3-hydroxy-5-methoxyisonicotinaldehyde (420 mg, 17%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 10.96 (s, 1H), 10.26 (s, 1H), 7.96 (s, 1H), 7.80 (s, 1H), 3.84 (s, 3H). LRMS (M+H+) m/z 154.1.

Workup

  1. temperatureThe mixture was reflux O/N
  2. extractionThe aqueous layer was extracted with DCM three times
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated
  5. custompurified on silica gel using
  6. additiona mixture of EtOAc and hexanes as eluent

Sources & evidence

ORD record
ord-9575f126ac8744a49dbb82a94e6911d1
Source dataset
uspto-grants-2015_04
Patent number
US09012450B2

Reaction notes

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