Hydrochloric Acid → HCID 76710730, compound

HRID 1188944Notes

Reaction equation

HRID 1188944 reaction equation
[CH3:1][O:2][C:3]1[CH:9]=[C:8]([O:10][C:11]2[CH:12]=[N:13][C:14]([CH2:17][O:18][CH3:19])=[CH:15][CH:16]=2)[CH:7]=[CH:6][C:4]=1[NH2:5].Cl.[N:21]([O-])=O.[Na+].[OH-].[K+].[CH3:27][CH:28](C(=O)C)[C:29]([O:31][CH2:32][CH3:33])=[O:30]>O.C(O)C.C(#N)C>[CH3:1][O:2][C:3]1[CH:9]=[C:8]([O:10][C:11]2[CH:12]=[N:13][C:14]([CH2:17][O:18][CH3:19])=[CH:15][CH:16]=2)[CH:7]=[CH:6][C:4]=1[NH:5][N:21]=[C:28]([CH3:27])[C:29]([O:31][CH2:32][CH3:33])=[O:30]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 701Ethyl 2-methylacetoacetateHCID 14797Potassium HydroxideHCID 23668193Sodium NitriteHCID 58237096HCID 58237096, compound

Product 1

HCID 76710730HCID 76710730, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 2-methoxy-4-{[6-(methoxymethyl)pyridin-3-yl]oxy}aniline (20.1 g), ethanol (300 mL) and acetonitrile (30 mL) was added concentrated hydrochloric acid (14.2 mL) at 5° C. A solution of sodium nitrite (6.39 g) in water (20 mL) was added dropwise to the mixture at 5° C. The whole was stirred at room temperature for 30 min. The mixture was added to the mixture of potassium hydroxide (85%, 15.2 g), ethyl 2-methyl-3-oxobutanoate (12.2 g), ethanol (60 mL) and water (60 mL) at −20 to −10° C. over a period of 15 min. The whole was stirred at −20° C. for 30 min. Water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate:hexane=2:3 to 2:1, volume ratio) to give the title compound (12.58 g, 44%) as a brown oil. MS 374 (MH+).

Workup

  1. stirringThe whole was stirred at −20° C. for 30 min
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography (ethyl acetate:hexane=2:3 to 2:1, volume ratio)

Sources & evidence

ORD record
ord-42a2d632002c4e90a6d999643a69963c
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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