Hydrochloric Acid → 6-Chloro-2-{3,3,3-trifluoro-2-[3-(3-trifluoromethyl-phenyl)-piperidin-1-ylmethyl]-propyl}-benzooxazole hydrochloride

HRID 1051396Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1051396
[F:1][C:2]([F:26])([F:25])[CH:3]([CH2:8][N:9]1[CH2:14][CH2:13][CH2:12][CH:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[CH2:10]1)[CH2:4][C:5](O)=O.[NH2:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[OH:35].C1(C)C=CC(S(O)(=O)=O)=CC=1.Cl>C1(C)C=CC=CC=1.C(OCC)(=O)C.CCOCC.CCCCCC>[ClH:34].[Cl:34][C:31]1[CH:32]=[CH:33][C:28]2[N:27]=[C:5]([CH2:4][CH:3]([CH2:8][N:9]3[CH2:14][CH2:13][CH2:12][CH:11]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:22])[F:23])[CH:16]=4)[CH2:10]3)[C:2]([F:26])([F:25])[F:1])[O:35][C:29]=2[CH:30]=1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 915912-Amino-5-chlorophenolHCID 901035704,4,4-Trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanoic acid

Produkt 1

HCID 752021606-Chloro-2-{3,3,3-trifluoro-2-[3-(3-trifluoromethyl-phenyl)-piperidin-1-ylmethyl]-propyl}-benzooxazole hydrochlorideAusbeute 48,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 21584099Diethylether hexaneLösungsmittel

Reaktionsbedingungen

Temperatur
135 °C

Versuchsvorschrift

In a 5 mL microwave vial, 4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanoic acid (50 mg, 130 μmol), 2-amino-5-chlorophenol (28.1 mg, 196 μmol) and p-toluenesulfonic acid (4.96 mg, 26.1 μmol) were combined in toluene (1.00 ml) to give a dark brown suspension. The tube was sealed and heated in a microwave at 135° C. for 2 h, diluted with ethyl acetate (30 ml), washed with a saturated solution of Na2CO3 (30 ml) and H2O (30 ml), dried over MgSO4, filtered and concentrated in vacuo to give an oil. The oil was purified on a silica column (100% CH2Cl2 to 50% ethyl acetate/CH2Cl2 gradient) to afford an oil which was dissolved in ether/hexane (1 ml/1 ml), treated with a 4N HCl solution in dioxanes (0.02 ml) and concentrated to afford 25 mg (37%) of 6-chloro-2-{3,3,3-trifluoro-2-[3-(3-trifluoromethyl-phenyl)-piperidin-1-ylmethyl]-propyl}-benzooxazole hydrochloride as a light red solid. MH+=491.

Aufarbeitung

  1. customto give a dark brown suspension
  2. customThe tube was sealed
  3. washwashed with a saturated solution of Na2CO3 (30 ml) and H2O (30 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. customThe oil was purified on a silica column (100% CH2Cl2 to 50% ethyl acetate/CH2Cl2 gradient)
  9. customto afford an oil which
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-50b3c55c453b4dbfafee1028fc8f32c7
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388172B2

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