Ethyl 2-methylacetoacetate → HCID 87126376, compound

HRID 1042112Notes

Reaction equation

HRID 1042112 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][C:7]1[N:12]=[CH:11][C:10]([O:13][C:14]2[CH:20]=[CH:19][C:17]([NH2:18])=[C:16]([O:21][CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:15]=2)=[CH:9][CH:8]=1.[N:28]([O-])=O.[Na+].[CH3:32][CH:33](C(C)=O)[C:34]([O:36][CH2:37][CH3:38])=[O:35].[OH-].[K+]>Cl.C(#N)C.O.C(O)C.CCCCCC.C(OCC)(=O)C>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][C:7]1[N:12]=[CH:11][C:10]([O:13][C:14]2[CH:20]=[CH:19][C:17]([NH:18]/[N:28]=[C:33](\[CH3:32])/[C:34]([O:36][CH2:37][CH3:38])=[O:35])=[C:16]([O:21][CH:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[CH:15]=2)=[CH:9][CH:8]=1

Participants

11

Reactant 4

HCID 701Ethyl 2-methylacetoacetateHCID 14797Potassium HydroxideHCID 23668193Sodium NitriteHCID 66726077HCID 66726077, compound

Product 1

HCID 87126376HCID 87126376, compoundYield 59%

Reagents, catalysts & solvents 6

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-({6-[(2-Methoxyethoxy)methyl]pyridin-3-yl}oxy)-2-(tetrahydro-2H-pyran-4-yloxy)aniline (7.84 g) was dissolved in 2N hydrochloric acid (20 mL) and acetonitrile (15 mL), and aqueous solution (20 mL) of sodium nitrite (1.73 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 (3.17 g) and potassium hydroxide (3.3 g) in water (70 mL) and ethanol (70 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 (6.0 g, yield 59%) as a yellow oil.

Workup

  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

Sources & evidence

ORD record
ord-fc74e71f8d3249549e3e5b99c8052f4c
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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