Ethyl 2-methylacetoacetate → HCID 86624021, compound

HRID 643940Notes

Reaction equation

HRID 643940 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:6]([NH:8][CH:9]=[O:10])[CH:7]=1.N([O-])=O.[Na+].[CH2:23]([O:25][C:26](=[O:32])[CH:27](C)[C:28](C)=O)[CH3:24].[OH-].[K+].[Cl-].[Na+].C(OC(=O)C(=NNC1C=CC(OCC2C=CC=CC=2)=C(NC=O)C=1)C)C.C(OC(=O)C(N=NC1C=CC(OCC2C=CC=CC=2)=C(NC=O)C=1)(C)C(=O)C)C.C(=O)(O)[O-].[Na+]>Cl.C(O)=O>[CH2:23]([O:25][C:26]([C:27]1[NH:1][C:2]2[C:3]([CH:28]=1)=[CH:4][C:5]([O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[C:6]([NH:8][CH:9]=[O:10])[CH:7]=2)=[O:32])[CH3:24]

Participants

11

Reactant 8

HCID 701Ethyl 2-methylacetoacetateHCID 5234Sodium ChlorideHCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 23668193Sodium NitriteHCID 86624020HCID 86624020, compoundHCID 86624022HCID 86624022, compound2×HCID 86624023HCID 86624023, compound2×

Product 1

HCID 86624021HCID 86624021, compound

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 313Hydrochloric AcidSolvent

Procedure

To a solution of N-(5-amino-2-benzyloxyphenyl)-formamide (3.35 g, 13.8 mmol) in 0.3N HCl (91 mL) is added sodium nitrite (0.285 g, 4.13 mmol) at 0° C. The mixture is stirred for 0.5 h. This mixture is added to a solution prepared by mixing ethyl-2-methylacetoacetate (0.72 g, 4.99 mmol) with potassium hydroxide (0.28 g, 4.99 mmol) at 0° C. The combined mixture is stirred for ˜1 h. To the reaction mixture is added saturated aqueous sodium chloride and extracted with EtOAc. The combined organic extracts are washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated to afford a mixture of 2-[(4-benzyloxy-3-formylaminophenyl)-hydrazono]-propionic acid ethyl ester and 2-(4-benzyloxy-3-formylaminophenylazo)-2-methyl-3-oxo-butyric acid ethyl ester as a dark oil. The mixture of 2-[(4-benzyloxy-3-formylaminophenyl)-hydrazono]-propionic acid ethyl ester and 2-(4-benzyloxy-3-formylaminophenylazo)-2-methyl-3-oxo-butyric acid ethyl ester, is dissolved in formic acid (10 mL) and stirred at 80° C. for 4.5 h. The reaction mixture is neutralized with saturated sodium bicarbonate and the resulting mixture is extracted with EtOAc and washed with brine and water. The organic phase is separated and dried over MgSO4 and concentrated to afford 5-benzyloxy-6-formylamino-1H-indole-2-carboxylic acid ethyl ester as a grey solid: (M−H)−=337.1.

Workup

  1. additionThis mixture is added to a solution
  2. customprepared
  3. stirringThe combined mixture is stirred for ˜1 h
  4. extractionextracted with EtOAc
  5. washThe combined organic extracts are washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford
  10. stirringstirred at 80° C. for 4.5 h
  11. extractionthe resulting mixture is extracted with EtOAc
  12. washwashed with brine and water
  13. customThe organic phase is separated
  14. dry with materialdried over MgSO4
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-5e5073b8ff6d4e97b1837792a735e908
Source dataset
uspto-grants-2010_04
Patent number
US07700633B2

Reaction notes

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