Ethyl Acetoacetate → ethyl 2-methyl-1H-indole-3-carboxylate

HRID 642259

Reaktionsgleichung

Reaktionsgleichung von HRID 642259
I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH2:8].[Na].[C:10]([O:16][CH2:17][CH3:18])(=[O:15])[CH2:11][C:12]([CH3:14])=O>CN(C=O)C.C(OC)(C)(C)C.O.N>[CH2:17]([O:16][C:10]([C:11]1[C:2]2[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=2)[NH:8][C:12]=1[CH3:14])=[O:15])[CH3:18]

Komponenten

8

Edukt 3

HCID 8868Ethyl AcetoacetateHCID 119952-IodoanilineHCID 5360545Sodium

Produkt 1

HCID 4072358ethyl 2-methyl-1H-indole-3-carboxylateAusbeute 26,4 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 222AmmoniaLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 15413tert-Butyl methyl etherLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 2-iodo-phenylamine (44.30 g, 202 mmol), sodium salt of ethyl acetoacetate (42.1 g, 263 mmol), and Cu(I)I (50.1 g, 263 mmol) in DMF (200 mL) was stirred at 120° C. overnight. Then the reaction mixture was cooled to room temperature, then diluted with methyl tert-butyl ether (MTBE) and water, and concentrated ammonia was added to dissolve the solid, the two layers were separated, the water layer was back extracted with MTBE; all MTBEs were combined and washed with sat. NaCl aqueous solution, dried over anhydrous sodium sulfate, filtered, and concentrated sequentially. The residue was crystallized in hexanes/EtOAc, giving the desired product (10.84 g), the mother liquor was concentrated and purified on column to give an additional batch of product (4.76 g). The title compound, 1H NMR (200 MHz, CDCl3): δ (ppm)=8.32 (1H), 8.09 (m, 1H), 7.31-7.13 (m, 3H), 4.39 (q, 2H, J=6.8 Hz), 2.74 (s, 3H), 1.45 (t, 3H, J=6.8 Hz).

Aufarbeitung

  1. temperatureThen the reaction mixture was cooled to room temperature
  2. additionwas added
  3. dissolutionto dissolve the solid
  4. customthe two layers were separated
  5. extractionthe water layer was back extracted with MTBE
  6. washwashed with sat. NaCl aqueous solution
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated sequentially
  10. customThe residue was crystallized in hexanes/EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-afd5d3a8e9184f71b977a6b7f82c2303
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07696223B2

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