Dimethylformamide → 1-{2-[3-(4-Chlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]-3,3,3-trifluoro-propyl}-3-(3-trifluoromethyl-phenyl)-piperidine hydrochloride

HRID 1051403Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1051403
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[N:35][OH:36])[NH:9][C:10](=O)[CH2:11][CH:12](CN2CCCC(C3C=CC=C(C(F)(F)F)C=3)C2)[C:13]([F:16])([F:15])[F:14])=[CH:4][CH:3]=1.[CH3:37][N:38]([CH:40]=O)[CH3:39].[CH3:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47]>[Cl-].[Na+].O.O.O1CCOCC1>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([CH2:11][CH:12]([C:13]([F:14])([F:15])[F:16])[CH2:40][N:38]3[CH2:37][CH2:42][CH2:43][CH:44]([C:45]4[CH:7]=[CH:2][CH:3]=[C:47]([C:13]([F:16])([F:15])[F:14])[CH:46]=4)[CH2:39]3)[O:36][N:35]=2)=[CH:6][CH:7]=1

Komponenten

6

Edukt 3

HCID 6228DimethylformamideHCID 8058HexaneHCID 137210851N-((4-chlorophenyl)(hydroxyimino)methyl)-4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanamide

Produkt 1

HCID 752013751-{2-[3-(4-Chlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]-3,3,3-trifluoro-propyl}-3-(3-trifluoromethyl-phenyl)-piperidine hydrochlorideAusbeute 41 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 312751,4-DioxaneLösungsmittelHCID 23713072Sodium chloride dihydrateLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

In a 5 mL sealed tube, N-((4-chlorophenyl)(hydroxyimino)methyl)-4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanamide (30 mg, 56.0 μmol) was combined with DMF (2 ml) and heated at 120° C. for 3 hr. The reaction mixture was diluted with 30 ml of brine/water (1:1) and extracted with ether (2×30 ml). The combined organic layer was washed with brine and water, dried with MgSO4, filtered and concentrated in vacuo to give an oil. This crude material was purified by flash chromatography (silica gel, 12 g, 0% to 30% ethyl acetate in hexanes gradient) to afford an oil. This oil was treated with 4NHCl in dioxane and hexane and concentrated to give 14 mg (41%) of 1-{2-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]-3,3,3-trifluoro-propyl}-3-(3-trifluoromethyl-phenyl)-piperidine hydrochloride as a viscous solid. This solid was a 1:1 mixture of diastereomers by LCMS (MS of each peak showed MH+=518).

Aufarbeitung

  1. customIn a 5 mL sealed tube
  2. extractionextracted with ether (2×30 ml)
  3. washThe combined organic layer was washed with brine and water
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. customThis crude material was purified by flash chromatography (silica gel, 12 g, 0% to 30% ethyl acetate in hexanes gradient)
  9. customto afford an oil
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-17847cdcdf834128ba2cfd6d2d83889a
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388172B2

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