Hydrochloric Acid → ethyl (2E)-2-[[2-ethyl-4-[(6-methylsulfonyl-3-pyridinyl)oxy]phenyl]hydrazinylidene]propanoate

HRID 1042134Notes

Reaction equation

HRID 1042134 reaction equation
[CH2:1]([C:3]1[CH:9]=[C:8]([O:10][C:11]2[CH:12]=[N:13][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][CH:16]=2)[CH:7]=[CH:6][C:4]=1[NH2:5])[CH3:2].Cl.[N:22]([O-])=O.[Na+].[CH3:26][CH:27](C(C)=O)[C:28]([O:30][CH2:31][CH3:32])=[O:29].[OH-].[K+]>O.C(O)C.CCCCCC.C(OCC)(=O)C>[CH2:1]([C:3]1[CH:9]=[C:8]([O:10][C:11]2[CH:12]=[N:13][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][CH:16]=2)[CH:7]=[CH:6][C:4]=1[NH:5]/[N:22]=[C:27](\[CH3:26])/[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:2]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 701Ethyl 2-methylacetoacetateHCID 14797Potassium HydroxideHCID 23668193Sodium NitriteHCID 667259082-Ethyl-4-{[6-(methylsulfonyl)pyridin-3-yl]oxy}aniline

Product 1

HCID 87126290ethyl (2E)-2-[[2-ethyl-4-[(6-methylsulfonyl-3-pyridinyl)oxy]phenyl]hydrazinylidene]propanoateYield 66%

Reagents, catalysts & solvents 4

HCID 702EthanolSolvent2×HCID 962WaterSolvent3×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-7.5 °C

Procedure

A mixture of 2-ethyl-4-{[6-(methylsulfonyl)pyridin-3-yl]oxy}aniline (11.3 g), concentrated hydrochloric acid (6.8 mL), ethanol (150 mL), and water (15 mL) was cooled to −5 to −10° C., and aqueous solution (15 mL) of sodium nitrite (3.0 g) was added dropwise. After the completion of the dropwise addition, the mixture was stirred at the same temperature for 40 min. The reaction solution was added dropwise to a solution of ethyl 2-methylacetoacetate (6.1 mL) and potassium hydroxide (8.0 g) in water (100 mL) and ethanol (60 mL) at −5 to −10° C. After stirring at −10° C. for 30 min, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (ethyl acetate:hexane=25:75 to 40:60, volume ratio) to give the title compound (10.4 g, yield 66%) as a dark-red oil.

Workup

  1. additionAfter the completion of the dropwise addition
  2. stirringAfter stirring at −10° C. for 30 min
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained crude product

Sources & evidence

ORD record
ord-082369d5484549e7b4c877fc559467e8
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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