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Hydrazine → 1,1-dimethylethyl 4-[[5-(4-fluorophenyl)-4,5-dihydro-4-hydroxy-4-(4-pyridinyl)-1H-pyrazol-3-yl]methyl]-1-piperidinecarboxylate

HRID 1058041
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1058041
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:10][C:9]2([C:17](=O)[CH2:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)[C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.[NH2:33][NH2:34]>C(O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[NH:34][N:33]=[C:17]([CH2:18][CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])[CH2:21][CH2:20]3)[C:9]2([OH:10])[C:11]2[CH:12]=[CH:13][N:14]=[CH:15][CH:16]=2)=[CH:4][CH:3]=1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

4

Edukt 2

HCID 9321HydrazineHCID 220375811,1-Dimethylethyl 4-(2-[3-(4-fluorophenyl)-2-(4-pyridinyl)oxiranyl]-2-oxoethyl]-1-piperidinecarboxylate

Produkt 1

HCID 220375671,1-dimethylethyl 4-[[5-(4-fluorophenyl)-4,5-dihydro-4-hydroxy-4-(4-pyridinyl)-1H-pyrazol-3-yl]methyl]-1-piperidinecarboxylateAusbeute 53,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Versuchsvorschrift

To a solution of 1,1-dimethylethyl 4-[2-[3-(4-fluorophenyl)-2-(4-pyridinyl)oxiranyl]-2-oxoethyl]-1-piperidinecarboxylate prepared in step 4 of this Example (3.45 g, 7.8409 mmol) in ethanol (15 mL), anhydrous hydrazine (0.50 mL, 15.6818 mmol) was added. The reaction was heated to reflux overnight. The reaction solution was cooled to room temperature and ethanol was removed under reduced pressure. The resulting residue was taken into ethyl acetate, washed with water and brine, and dried over MgSO4. After filtration the solvent was removed under reduced pressure. The crude residue was purified by chromatography (silica gel, 2:1-1:1-1:2 hexane/ethyl acetate) to give 1,1-dimethylethyl 4-[[5-(4-fluorophenyl)-4,5-dihydro-4-hydroxy-4-(4-pyridinyl)-1H-pyrazol-3-yl]methyl]-1-piperidinecarboxylate (1.9187 g, 53.9%). This intermediate (1.8611 g, 4.0993 mmol) was dissolved in dry methylene chloride (40 mL) and treated with Martin sulfurane dehydrating reagent (4.13 g, 6.1490 mmol). The reaction solution was stirred at room temperature under N2 overnight, then diluted with ethyl acetate, washed with 1N sodium hydroxide solution, water and brine, dried over MgSO4. After filtration the solvents were removed. The resulting crude product mixture was purified by flash chromatoghaphy (silica gel, 2:1-1:1-1:2 Hexane/ethyl acetate) to give 1,1-dimethylethyl 4-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]methyl]-1-piperidinecarboxylate (0.6964 g, 39%)

Aufarbeitung

  1. temperatureThe reaction was heated
  2. temperatureto reflux overnight
  3. customethanol was removed under reduced pressure
  4. washwashed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationAfter filtration the solvent
  7. customwas removed under reduced pressure
  8. customThe crude residue was purified by chromatography (silica gel, 2:1-1:1-1:2 hexane/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-1913a8624e1d419498dc0c8b24598852
Quelldatensatz
uspto-grants-2003_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US06514977B1

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