Hydrochloric Acid → 3-(3-Chlorobenzoyl)-2-ethylaminopyridine-6-carbaldehyde

HRID 368980Notes

Reaction equation

HRID 368980 reaction equation
[Mg].BrC1C=C(Cl)C=CC=1.C(C1C(NCC)=NC(C(OC)OC)=CC=1)#N.[Cl-].[NH4+].[Cl:28][C:29]1[CH:30]=[C:31]([CH:48]=[CH:49][CH:50]=1)[C:32]([C:34]1[C:35]([NH:45][CH2:46][CH3:47])=[N:36][C:37]([CH:40](OC)[O:41]C)=[CH:38][CH:39]=1)=[O:33].Cl.[OH-].[Na+]>O1CCCC1>[Cl:28][C:29]1[CH:30]=[C:31]([CH:48]=[CH:49][CH:50]=1)[C:32]([C:34]1[C:35]([NH:45][CH2:46][CH3:47])=[N:36][C:37]([CH:40]=[O:41])=[CH:38][CH:39]=1)=[O:33]

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 79281-Bromo-3-chlorobenzeneHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 227166793-(3-Chlorobenzoyl)-2-ethylamino-6-dimethoxymethylpyridineHCID 232844663-Cyano-2-ethylamino-6-dimethoxymethylpyridine

Product 1

HCID 232844713-(3-Chlorobenzoyl)-2-ethylaminopyridine-6-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Magnesium (18.6 g, 0.76 mol) was added to 500 ml of tetrahydrofuran in which 146.7 g (0.77 mol) of 3-bromochlorobenzene had been dissolved, followed by stirring at room temperature. Since exothermic reaction occurred, the stirring was continued until the exothermicity ceased. The reaction solution was cooled to -20° C., mixed with 33.9 g (0.15 mol) of 3-cyano-2-ethylamino-6-dimethoxymethylpyridine and then heated-overnight under reflux. The reaction solution was mixed with saturated ammonium chloride aqueous solution and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. After removing magnesium sulfate by filtration, the solvent was evaporated under a reduced pressure to give crude 3-(3-chlorobenzoyl)-2-ethylamino-6-dimethoxymethylpyridine. The crude 3-(3-chlorobenzoyl)-2-ethylamino-6-dimethoxymethylpyridine was diluted with 500 ml of tetrahydrofuran, mixed with 6 N hydrochloric acid and then stirred at room temperature for 6 hours. The reaction mixture was adjusted to pH 10 with sodium hydroxide aqueous solution and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, magnesium sulfate was removed by filtration and then the resulting filtrate was concentrated under a reduced pressure. Thereafter, the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give 3-(3-chlorobenzoyl)-2-ethylaminopyridine-6-carbaldehyde. Reference Exampel 45

Workup

  1. dissolutionhad been dissolved
  2. customSince exothermic reaction
  3. temperatureThe reaction solution was cooled to -20° C.
  4. temperatureheated-overnight
  5. temperatureunder reflux
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customAfter removing magnesium sulfate
  10. filtrationby filtration
  11. customthe solvent was evaporated under a reduced pressure
  12. customto give crude 3-(3-chlorobenzoyl)-2-ethylamino-6-dimethoxymethylpyridine
  13. stirringstirred at room temperature for 6 hours
  14. extractionextracted with ethyl acetate
  15. dry with materialThe organic layer was dried over anhydrous magnesium sulfate, magnesium sulfate
  16. customwas removed by filtration
  17. concentrationthe resulting filtrate was concentrated under a reduced pressure
  18. customThereafter, the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-42e670c1a55a4d0f89f5ca6591c2b814
Source dataset
uspto-grants-2000_10
Patent number
US06136810

Reaction notes

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