Ethyl 2-methylacetoacetate → ethyl 5-methyl-1H-indole-2-carboxylate

HRID 844435Notes

Reaction equation

HRID 844435 reaction equation
N([O-])=O.[Na+].[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=1.C([O-])(=O)C.[Na+].[CH3:18][CH:19](C(=O)C)[C:20]([O:22][CH2:23][CH3:24])=[O:21].[OH-].[K+].[Na+].[Cl-]>O.Cl.C(O)C>[CH3:12][C:9]1[CH:8]=[C:7]2[C:6](=[CH:11][CH:10]=1)[NH:5][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18]2

Participants

10

Reactant 6

HCID 701Ethyl 2-methylacetoacetateHCID 5234Sodium ChlorideHCID 7813p-ToluidineHCID 14797Potassium HydroxideHCID 517045Sodium AcetateHCID 23668193Sodium Nitrite

Product 1

HCID 232919ethyl 5-methyl-1H-indole-2-carboxylateYield 29.6%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent3×

Conditions

Temperature
0 °C

Procedure

15.4 g of NaNO2 in 4 ml of water are added, at 0° C., to 23.57 g of p-toluidine in 50 ml of HCl and 100 ml of water; after stiring for 20 minutes, 18.2 g of sodium acetate ate added. Separately, a mixture of 28.8 g of ethyl 2-methyl-3-oxobutyrate in 100 ml of ethanol is prepared, at 0° C, and is treated with 11.22 g of potassium hydroxide in20 ml of water and 200 g of crushed ice. The diazonium salt solution prepared above is added and the mixture is left stirring for 3 hours at 0° C. After leaving overnight in a refrigerator, it is poured onto saturated NaCl solution and is then extracted with EtOAc, dried over MgSO4 and concentrated. The residue is taken up in toluene, 16 g of para-toluenesulphonic acid are added and the mixture is refluxed overnight, eliminating the water using Dean-Stark apparatus. The reaction medium is chromatographed on silica, eluting with toluene, to give 12 g of the expected product: m.p.=133° C.

Workup

  1. customis prepared, at 0° C
  2. additionabove is added
  3. waitthe mixture is left
  4. customAfter leaving overnight in a refrigerator, it
  5. extractionis then extracted with EtOAc
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. addition16 g of para-toluenesulphonic acid are added
  9. temperaturethe mixture is refluxed overnight
  10. customThe reaction medium is chromatographed on silica
  11. washeluting with toluene

Sources & evidence

ORD record
ord-92d61ace23b54d4fafba6219cfa940ef
Source dataset
uspto-grants-2002_04
Patent number
US06380230B1

Reaction notes

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