1,2-Dichloroethane → (2S3S)-N-{[2-Cyclopropoxy-5-(trifluoromethoxy)phenyl]methyl}-2-phenylpiperidin-3-amine Dihydrochloride

HRID 323763

Reaktionsgleichung

Reaktionsgleichung von HRID 323763
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH:15]1([O:18][C:19]2[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][C:20]=2[CH:21]=O)[CH2:17][CH2:16]1.[C:32]1([C@H:38]2[C@@H:43]([NH2:44])[CH2:42][CH2:41][CH2:40][NH:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(O)(=O)C.C(=O)([O-])O.[Na+].[Cl:54]CCCl>>[ClH:54].[ClH:54].[CH:15]1([O:18][C:19]2[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][C:20]=2[CH2:21][NH:44][C@H:43]2[CH2:42][CH2:41][CH2:40][NH:39][C@H:38]2[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:17][CH2:16]1

Komponenten

7

Edukt 6

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 9812908(2S,3S)-2-phenylpiperidin-3-amineHCID 215840762-Cyclopropoxy-5-(trifluoromethoxy)benzaldehyde

Produkt 1

HCID 86756609(2S3S)-N-{[2-Cyclopropoxy-5-(trifluoromethoxy)phenyl]methyl}-2-phenylpiperidin-3-amine DihydrochlorideAusbeute 46 %

Versuchsvorschrift

Sodium triacetoxyborohydride (411 mg, 1.94 mmol) was added to a mixture of 2-cyclopropoxy-5-(trifluoromethoxy)benzaldehyde (Description 9, 159 mg, 0.646 mmol), (2S3S)-2-phenylpiperidin-3-amine (prepared by the method described in WO 95/08549, 171 mg, 0.97 mmol) and acetic acid, (111 μl, 1.94 mmol) in 1,2-dichloroethane (5 mL) and the mixture was stirred at room temperature for 2.5 h. The mixture was poured into aqueous sodium hydrogen carbonate (satd., 50 mL) and extracted with ethyl acetate. The combined organic fractions were washed with aqueous sodium hydrogen carbonate (satd., 2×50 mL) and brine (50 mL), dried (Na2SO4) and the solvent was evaporated under reduced pressure. The residue was purified by MPLC on silica gel, eluting with CH2Cl2/MeOH/NH3(Aq.) (97:3:0.3). The residue was dissolved in ethanol (2 mL) and ethanolic hydrogen chloride (5M, 0.5 mL) was added. The solid was collected and recrystallised from ethanol. The solid was collected and dried in vacuo to give the title compound as a yellow solid (144 mg, 46%). m.p. 168-171° C. 1H NMR (360 MHz, CD3OD) δ0.66-0.67 (1H, m), 0.80-0.82 (3H, m), 1.99-2.03 (1H, m), 2.27-2.35 (1H, m), 2.43-2.54 (2H, m), 3.30 (1H, m), 3.57-3.68 (1H, m), 3.75-3.80 (2H, m), 4.06-4.14 (2H, m), 5.05-5.06 (1H, d, J 2.7 Hz), 7.26 (1H, d, J 2.0 Hz), 7.30-7.39 (2H, m), 7.50-7.57 (3H, m), and 7.61 (2H, m). m/z (ES+) 407 (M+1).

Aufarbeitung

  1. customprepared by the method
  2. extractionextracted with ethyl acetate
  3. washThe combined organic fractions were washed with aqueous sodium hydrogen carbonate (satd., 2×50 mL) and brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by MPLC on silica gel
  7. washeluting with CH2Cl2/MeOH/NH3(Aq.) (97:3:0.3)
  8. dissolutionThe residue was dissolved in ethanol (2 mL)
  9. additionethanolic hydrogen chloride (5M, 0.5 mL) was added
  10. customThe solid was collected
  11. customrecrystallised from ethanol
  12. customThe solid was collected
  13. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-15a4c569cd77401b8343a80cecf76091
Quelldatensatz
uspto-grants-2001_04
Patentnummer
US06214846B1

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