Hydrochloric Acid → tert-butyl 4-[4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl] phenylaminocarbonyl]piperidine-1-carboxylate

HRID 1296477Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1296477
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:17][C:18]([F:36])([F:35])[C:19]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[N:21]([C:28]2[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][CH:29]=2)[N:20]=1.Cl.C1COCC1>C(OCC)(=O)C>[F:36][C:18]([F:17])([F:35])[C:19]1[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[N:21]([C:28]2[CH:29]=[CH:30][C:31]([NH:32][C:14]([CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]3)=[O:16])=[CH:33][CH:34]=2)[N:20]=1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 27406684-(3,5-Bis(trifluoromethyl)-1H-pyrazol-1-yl)aniline

Produkt 1

HCID 22288408tert-butyl 4-[4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl] phenylaminocarbonyl]piperidine-1-carboxylateAusbeute 78,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 1-tert-butoxycarbonylpiperidine-4-carboxylic acid (198 mg), 4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)aniline (206 mg), WSCD hydrochloride (172 mg) and THF (3 ml) was stirred overnight at room temperature. After adding ethyl acetate, the reaction solution was washed with water, saturated sodium bicarbonate aqueous solution, 1 N hydrochloric acid and saturated brine in that order. The organic layer was dried over anhydrous sodium sulfate and then concentrated under a reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=7:1-5:1) to give tert-butyl 4-[4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenylaminocarbonyl]piperidine-1-carboxylate (279 mg) as a colorless amorphous solid. 4 N Hydrochloric acid ethyl acetate solution (2.60 ml) was added to a mixture of this solid (263 mg) and ethyl acetate (2.6 ml), followed by stirring at room temperature for 2 hours and 45 minutes. The reaction solution was concentrated under a reduced pressure, diethyl ether was added to the thus obtained residue, and the mixture was concentrated under a reduced pressure. By recrystallizing the resulting residue from a mixed solvent of ethyl acetate and n-hexane, (4′-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]piperidine-4-carboxyanilide hydrochloride (201 mg) was obtained as colorless powder crystals.

Aufarbeitung

  1. washthe reaction solution was washed with water, saturated sodium bicarbonate aqueous solution, 1 N hydrochloric acid and saturated brine in that order
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under a reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=7:1-5:1)

Quellen und Nachweise

ORD-Eintrag
ord-56c4440872e54eda8c19e309401d3c0c
Quelldatensatz
uspto-grants-2007_07
Patentnummer
US07247635B2

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