Ethyl 2-methylacetoacetate → ethyl (2E)-2-[[4-[[6-(methylsulfonylmethyl)-3-pyridinyl]oxy]-2-(oxan-4-yloxy)phenyl]hydrazinylidene]propanoate

HRID 1042118Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1042118
[CH3:1][S:2]([CH2:5][C:6]1[N:11]=[CH:10][C:9]([O:12][C:13]2[CH:19]=[CH:18][C:16]([NH2:17])=[C:15]([O:20][CH:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[CH:14]=2)=[CH:8][CH:7]=1)(=[O:4])=[O:3].[N:27]([O-])=O.[Na+].[CH3:31][CH:32](C(C)=O)[C:33]([O:35][CH2:36][CH3:37])=[O:34].[OH-].[K+]>Cl.C(#N)C.O.C(O)C.CCCCCC.C(OCC)(=O)C>[CH3:1][S:2]([CH2:5][C:6]1[N:11]=[CH:10][C:9]([O:12][C:13]2[CH:19]=[CH:18][C:16]([NH:17]/[N:27]=[C:32](\[CH3:31])/[C:33]([O:35][CH2:36][CH3:37])=[O:34])=[C:15]([O:20][CH:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[CH:14]=2)=[CH:8][CH:7]=1)(=[O:3])=[O:4]

Komponenten

11

Edukt 4

HCID 701Ethyl 2-methylacetoacetateHCID 14797Potassium HydroxideHCID 23668193Sodium NitriteHCID 667261624-({6-[(Methylsulfonyl)methyl]pyridin-3-yl}oxy)-2-(tetrahydro-2H-pyran-4-yloxy)aniline

Produkt 1

HCID 87126381ethyl (2E)-2-[[4-[[6-(methylsulfonylmethyl)-3-pyridinyl]oxy]-2-(oxan-4-yloxy)phenyl]hydrazinylidene]propanoateAusbeute 99 %

Reagenzien, Katalysatoren, Lösungsmittel 6

HCID 313Hydrochloric AcidLösungsmittelHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel2×HCID 6342AcetonitrileLösungsmittelHCID 8058HexaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

4-({6-[(Methylsulfonyl)methyl]pyridin-3-yl}oxy)-2-(tetrahydro-2H-pyran-4-yloxy)aniline (21 g) was dissolved in 2N hydrochloric acid (55 mL) and acetonitrile (20 mL), and aqueous solution (50 mL) of sodium nitrite (4.59 g) was added dropwise under ice-cooling. After the completion of the dropwise addition, the reaction mixture was stirred under ice-cooling for 30 min. The reaction mixture was added dropwise to a solution of ethyl 2-methylacetoacetate (8.4 g) and potassium hydroxide (8.8 g) in water (100 mL) and ethanol (100 mL) at −20° C. After stirring at −20° C. for 30 min, water was added to the reaction mixture, 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=0:100 to 85:15, volume ratio) to give the title compound (27 g, yield 99%) as a yellow amorphous solid.

Aufarbeitung

  1. temperaturecooling
  2. additionAfter the completion of the dropwise addition
  3. temperaturecooling for 30 min
  4. stirringAfter stirring at −20° C. for 30 min
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained crude product

Quellen und Nachweise

ORD-Eintrag
ord-b987a8069790417ea09b34148505fdf4
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08557805B2

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