Ammonium Acetate → 4-[1-Hydroxy-5-(2-methylthiopyrimidin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl ester

HRID 342688Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 342688
[CH3:1][S:2][C:3]1[N:8]=[C:7]([C:9](=[N:22][OH:23])[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)=O)[CH:6]=[CH:5][N:4]=1.[C:24]([N:34]1[CH2:39][CH2:38][CH:37]([CH:40]=O)[CH2:36][CH2:35]1)([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25].C([O-])(=O)C.[NH4+:46]>C(O)(=O)C>[CH2:27]([O:26][C:24]([N:34]1[CH2:39][CH2:38][CH:37]([C:40]2[N:22]([OH:23])[C:9]([C:7]3[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=3)=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=3)[N:46]=2)[CH2:36][CH2:35]1)=[O:25])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Komponenten

5

Edukt 3

HCID 517165Ammonium AcetateHCID 2776272Benzyl 4-formylpiperidine-1-carboxylateHCID 1363653261-(2-Methylthiopyrimidin-4-yl)-2-(3-trifluoromethylphenyl)ethane-1,2-dione-1-oxime

Produkt 1

HCID 107693624-[1-Hydroxy-5-(2-methylthiopyrimidin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl esterAusbeute 114,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Versuchsvorschrift

To a mixture of 1-(2-methylthiopyrimidin-4-yl)-2-(3-trifluoromethylphenyl)ethane-1,2-dione-1-oxime (5.0 g, 0.0146 mole) and N-carbobenzyloxypiperidine-4-carboxaldehyde [Amici et al Eur. J. Med. Chem. 26, 625-631 (1991)] (4.70 g, 0.019 mole), in acetic acid (140 mL) was added ammonium acetate (23 g, 0.295 mole). The mixture was heated to reflux for 11/2 hours, cooled and concentrated to remove most of the acetic acid. The residue was dissolved in water (200 mL) and ethyl acetate (400 mL) and the pH adjusted to 7.5 with 3N sodium hydroxide. The ethyl acetate layer was removed, dried over Na2SO4, filtered and concentrated to give an oil (9.5 g crude product). The oil was used in the next step without further purification.

Aufarbeitung

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 11/2 hours
  3. temperaturecooled
  4. concentrationconcentrated
  5. customto remove most of the acetic acid
  6. dissolutionThe residue was dissolved in water (200 mL)
  7. customThe ethyl acetate layer was removed
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-c7f3db546c5d406ba0d3c74dfa64d211
Quelldatensatz
uspto-grants-1999_01
Patentnummer
US05859041

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