Trifluoroacetic acid → HCID 58992709, Verbindung

HRID 602159

Reaktionsgleichung

Reaktionsgleichung von HRID 602159
C(O[C:6]([NH:8][CH:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:24]=[CH:23][CH:22]=[CH:21][C:16]=2[C:17]([O:19][CH3:20])=[O:18])[CH2:10]1)=[O:7])(C)(C)C.FC(F)(F)C(O)=O.[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][C:42](C(O)=O)=[CH:41][CH:40]=2)=[CH:35][CH:34]=1.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>ClCCl.C(OCC)(=O)C>[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([C:39]2[CH:44]=[CH:43][C:42]([C:6]([NH:8][CH:9]3[CH2:14][CH2:13][CH2:12][N:11]([C:15]4[CH:24]=[CH:23][CH:22]=[CH:21][C:16]=4[C:17]([O:19][CH3:20])=[O:18])[CH2:10]3)=[O:7])=[CH:41][CH:40]=2)=[CH:37][CH:38]=1

Komponenten

9

Edukt 6

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 6160024-Biphenylcarboxylic acid, 4'-chloro-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 58992635HCID 58992635, Verbindung

Produkt 1

HCID 58992709HCID 58992709, VerbindungAusbeute 71,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Methyl 2-[3-(tert-butoxycarbonylamino)piperidin-1-yl]benzoate (2.34 g, 7.00 mmol) was dissolved in anhydrous dichloromethane (50 mL). While this solution was ice-chilled and stirred, trifluoroacetic acid (5.2 mL, 6.82 mmol) was added and the mixture was stirred for 3 hours. Subsequently, the reaction mixture was concentrated and a 10% hydrochloric acid/methanol mixture (50 mL) was added to the residue. The mixture was stirred at room temperature for 1 hour and was concentrated. The same process was repeated 3 times and the resulting solid were washed with ethyl acetate. This gave 1.33 g of a colorless powder. This product (113 mg) was dissolved in N,N-dimethylformamide (4 mL). While the solution was chilled to 0° C. and stirred, 4′-chlorobiphenyl-4-carboxylic acid (103 mg, 0.443 mmol), 1-hydroxybenzotriazole monohydrate (63.8 mg, 0.417 mmol), N-methylmorpholine (160 μL, 1.46 mmol) and 3-(3-dimethylaminopropyl)-1-ethylcarbodiimide hydrochloride (78.0 mg, 0.407 mmol) were added. The mixture was stirred at 0° C. for 20 min and at room temperature for the following 6 hours. Subsequently, the reaction mixture was diluted with ethyl acetate. The organic layer washed sequentially with 5% aqueous citric acid, a saturated aqueous sodium bicarbonate solution, water and brine. The washed product was dried over anhydrous sodium sulfate and the solvent was concentrated. Purification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=3:1) gave 142 mg of the desired compound as colorless crystals.

Aufarbeitung

  1. temperaturechilled
  2. stirringthe mixture was stirred for 3 hours
  3. concentrationSubsequently, the reaction mixture was concentrated
  4. additiona 10% hydrochloric acid/methanol mixture (50 mL) was added to the residue
  5. stirringThe mixture was stirred at room temperature for 1 hour
  6. concentrationwas concentrated
  7. washthe resulting solid were washed with ethyl acetate
  8. dissolutionThis product (113 mg) was dissolved in N,N-dimethylformamide (4 mL)
  9. stirringstirred
  10. stirringThe mixture was stirred at 0° C. for 20 min and at room temperature for the following 6 hours
  11. washThe organic layer washed sequentially with 5% aqueous citric acid
  12. dry with materialThe washed product was dried over anhydrous sodium sulfate
  13. concentrationthe solvent was concentrated
  14. customPurification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=3:1)

Quellen und Nachweise

ORD-Eintrag
ord-74b666a198c34a96a86e05a81eef2c10
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902367B2

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