Acetic Acid → Entacapone Impurity 9

HRID 132018

Reaktionsgleichung

Reaktionsgleichung von HRID 132018
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([N+:13]([O-:15])=[O:14])[C:11]=1[OH:12])[CH:7]=O)C.C(N[N:19](NCC)[C:20](=[O:24])[CH2:21][C:22]#[N:23])C.[C:28](O)(=O)[CH3:29].N1CCC[CH2:34][CH2:33]1>C1(C)C=CC=CC=1>[CH2:33]([N:19]([CH2:28][CH3:29])[C:20](=[O:24])[C:21]([C:22]#[N:23])=[CH:7][C:6]1[CH:9]=[C:10]([N+:13]([O-:15])=[O:14])[C:11]([OH:12])=[C:4]([O:3][CH3:1])[CH:5]=1)[CH3:34]

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehyde2×HCID 866114042-cyano-N,N-bis(ethylamino)acetamide

Produkt 1

HCID 67020297Entacapone Impurity 9Ausbeute 162 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
107.5 °C

Versuchsvorschrift

A flask was charged with 3-methoxy-4-hydroxy-5-nitrobenzaldehyde (25 g, 0.126 mole) (formula 2 where R is methyl) and N,N-diethylaminocyanoacetamide (formula (3)) (22.2 g, 0.158 mole), acetic acid (4.18 g) and piperidine (5.94 g), along with toluene (250 mL) and was heated to a reflux temperature of about 105-110° C. Water was removed azeotrophically for 15 hours. The reaction mixture was concentrated and quenched into dilute hydrochloric acid and chilled water (375 mL), and stirred for 3 hours. The precipitated solid was filtered and dried to provide 36 g (88.95% yield, HPLC purity of 94.2% (including isomer)) of the N,N-diethyl-2-cyano-3-(3-methoxy-4-hydroxy-5-nitrophenyl)acrylamide, which was used as such for the next stage.

Aufarbeitung

  1. customWater was removed azeotrophically for 15 hours
  2. concentrationThe reaction mixture was concentrated
  3. customquenched into dilute hydrochloric acid
  4. temperaturechilled water (375 mL)
  5. filtrationThe precipitated solid was filtered
  6. customdried

Quellen und Nachweise

ORD-Eintrag
ord-c0c4ef51be6f4c81bd6f0dd9cfc72a5f
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07385072B2

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