Ethyl cyanoacetate → Ethyl 2-amino-4-(3,4,5-trimethoxyphenyl)-3-thiophenecarboxylate

HRID 1944627Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1944627
[C:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].[CH3:9][O:10][C:11]1[CH:12]=[C:13]([C:21](=O)[CH3:22])[CH:14]=[C:15]([O:19][CH3:20])[C:16]=1[O:17][CH3:18].N1CCOCC1.BrC1C=CC2OC(C(NC3[S:43]C=C(C4C=CC(Cl)=CC=4)C=3C(O)=O)=O)=NC=2C=1>C1(C)C=CC=CC=1>[NH2:2][C:1]1[S:43][CH:22]=[C:21]([C:13]2[CH:12]=[C:11]([O:10][CH3:9])[C:16]([O:17][CH3:18])=[C:15]([O:19][CH3:20])[CH:14]=2)[C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5]

Komponenten

6

Edukt 4

HCID 7764Ethyl cyanoacetateHCID 8083MorpholineHCID 143453',4',5'-TrimethoxyacetophenoneHCID 595359892-(5-Bromobenzo[d]oxazole-2-carboxamido)-4-(4-chlorophenyl)thiophene-3-carboxylic acid

Produkt 1

HCID 299299Ethyl 2-amino-4-(3,4,5-trimethoxyphenyl)-3-thiophenecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Ethyl cyanoacetate (5 mmol), and 1-(3,4,5-trimethoxyphenyl)ethanone (5 mmol) are dissolved in toluene (5 mL). Morpholine (5 mmol) is added followed by activated molecular sieves (4A). The reaction is stirred at 80° C. for 12 hours. The reaction is cooled to room temperature, filtered and concentrated. The residue is taken up in toluene (5 mL), ethanol (5 mL) and sulfur is added (0.16 g; 5 mmol). The reaction mixture is heated with mixing at 70° C. for 12 hours. The reaction is cooled to room temperature and the solvents are evaporated. The residue is purified by HPLC to provide ethyl 2-amino-4-(3,4,5-trimethoxyphenyl)thiophene-3-carboxylate. Ethyl 2-amino-4-(3,4,5-trimethoxyphenyl)thiophene-3-carboxylate (5 mmol) is treated with 4-methylbenzoyl chloride (5 mmol) in THF (10 mL). The reaction is stirred at room temperature for 10 hours. The reaction is diluted with 1N NaOH (10 mL) and ethyl acetate (15 mL). The layers are separated, the organic layer is dried with anhydrous sodium sulfate, filtered and concentrated. The residue is purified by flash chromatography to provide ethyl 4-p-tolyl-2-(3,4,5-trimethoxybenzamido)thiophene-3-carboxylate. Ethyl 4-p-tolyl-2-(3,4,5-trimethoxybenzamido)thiophene-3-carboxylate is hydrolyzed under a variety of conditions (e.g. LiOH, water; LiOH, H2O2, water; or NaOH, water) to provide the title compound

Aufarbeitung

  1. temperatureThe reaction is cooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated
  4. additionethanol (5 mL) and sulfur is added (0.16 g; 5 mmol)
  5. temperatureThe reaction mixture is heated
  6. additionwith mixing at 70° C. for 12 hours
  7. temperatureThe reaction is cooled to room temperature
  8. customthe solvents are evaporated
  9. customThe residue is purified by HPLC

Quellen und Nachweise

ORD-Eintrag
ord-466e428435324fb0a3a7628e74885bac
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08394848B2

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