Hydrochloric Acid → (1R,2S)-1-(3,4-difluorophenyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]propanol

HRID 962904Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 962904
Br.[F:2][C:3]1[CH:4]=[C:5]([C@:10]2([OH:18])[O:15][CH2:14][C@@H:13]([CH3:16])[NH:12][C@H:11]2[CH3:17])[CH:6]=[CH:7][C:8]=1[F:9].C(O)C.O.[BH4-].[Na+].Cl>O>[F:2][C:3]1[CH:4]=[C:5]([C@@H:10]([OH:18])[C@@H:11]([NH:12][C@H:13]([CH3:16])[CH2:14][OH:15])[CH3:17])[CH:6]=[CH:7][C:8]=1[F:9]

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 19096565Water ethanolHCID 67706270(2S, 3S, 5R)-2-(3,4difluorophenyl)-3,5-dimethyl-2-morpholinol hydrobromide

Produkt 1

HCID 54225803(1R,2S)-1-(3,4-difluorophenyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]propanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

To a solution of (2S, 3S, 5R)-2-(3,4-difluorophenyl)-3,5-dimethyl-2-morpholinol hydrobromide (25.4 g, 0.078 mole) in 50--50 ethanol-water (300 ml) was added a solution of sodium borohydride (11.9 g, 0.31 mole) in water (120 ml) at 0° C. The resulting mixture was stirred for 16 hours at room temperature. The reaction mixture was treated with concentrated hydrochloric acid and concentrated under reduced pressure. The residue was dissolved in water, basified (40% aqueous sodium hydroxide), and extracted with dichloromethane. The organic layers were combined, washed with brine and dried (potassium carbonate) to give a solution of (1R, 2S)-1-(3,4-difluorophenyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]propanol in dichlomethane (500 ml). 50 ml of the solution was concentrated under reduced pressure to yield 1.9 g of the free base as a white solid. The free base was dissolved in diethyl ether and treated with ethereal hydrogen chloride. The hydrochloride salt was recrystallized from ethanol-diethyl ether mixtures to give 1.1 g of (1R, 2S)-1-(3,4-difluorophenyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]propanol hydrochloride as a white solid. m.p. 116°-117° C.

Aufarbeitung

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in water
  3. extractionextracted with dichloromethane
  4. washwashed with brine
  5. dry with materialdried (potassium carbonate)

Quellen und Nachweise

ORD-Eintrag
ord-8e2967cdbf7045c198117a51160f464c
Quelldatensatz
uspto-grants-1998_06
Patentnummer
US05760224

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