Acetamide → Isopropyl (2R,3S)-3-Acetamido-2-hydroxy-3-phenylpropanoate

HRID 1635685

Reaktionsgleichung

Reaktionsgleichung von HRID 1635685
O.[OH-].[Li+].CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C([O:25]C)C=C4)N(CC2)C1.[C:62]([NH2:65])(=[O:64])[CH3:63].[C:66]([O:76][CH:77]([CH3:79])[CH3:78])(=[O:75])[CH:67]=[CH:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1.BrNC(=O)C>O.[Os](=O)(=O)(=O)=O.C(O)(C)(C)C>[C:62]([NH:65][C@@H:68]([C:69]1[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=1)[C@@H:67]([OH:25])[C:66]([O:76][CH:77]([CH3:79])[CH3:78])=[O:75])(=[O:64])[CH3:63]

Komponenten

9

Edukt 5

HCID 178AcetamideHCID 4353N-BromoacetamideHCID 24521Cinnamic Acid Isopropyl EsterHCID 168937Lithium hydroxide, monohydrateHCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazine

Produkt 1

HCID 10956433Isopropyl (2R,3S)-3-Acetamido-2-hydroxy-3-phenylpropanoate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 30318Osmium TetroxideKatalysatorHCID 962WaterLösungsmittel2×HCID 6386tert-ButanolLösungsmittel

Versuchsvorschrift

Lithium hydroxide-hydrate (236 mg, 5.63 mmol) and osmium tetroxide (53 mg, 0.210 mmol) are dissolved in a minimal amount of water. To this is added t-butanol (8 ml) and (DHQ)2PHAL (205 mg, 0.263 mmol) and the reaction mixture is stirred for 10 minutes. Water (12 mil) is added and the reaction mixture is cooled in an ice bath to less than 4°. Acetamide (311 mg, 5.26 mmol), isopropyl cinnamate (I, 1.00 g, 5.26 mmol), and N-bromoacetamide (795 mg, 5.63 mmol) respectively are added to the reaction mixture. The mixture is stirred until complete as measured by HPLC. The reaction mixture is quenched with a small amount of sodium sulfite (50 mg) and allowed to warm to 20-25°. Ethyl acetate (5 ml) is added and the reaction mixture is stirred for 30 minutes. The phases are separated and the aqueous layer is extracted three times with ethyl acetate (30 ml). The organic layers are combined and washed three times with saline (30 ml). The organic layer is dried with sodium sulfate and filtered through a small amount of silica. The mixture is concentrated on a rotary evaporator and the product is recrystallized from ethyl acetate/hexane to give the title compound; mp=104-106°; HMR (300 MHz, CDCl3) 1.30, 2.00, 3.20, 4.78, 5.05, 5.55, 6.23 and 7.35 δ.

Aufarbeitung

  1. temperaturethe reaction mixture is cooled in an ice bath to less than 4°
  2. stirringThe mixture is stirred until complete
  3. customThe reaction mixture is quenched with a small amount of sodium sulfite (50 mg)
  4. temperatureto warm to 20-25°
  5. additionEthyl acetate (5 ml) is added
  6. stirringthe reaction mixture is stirred for 30 minutes
  7. customThe phases are separated
  8. extractionthe aqueous layer is extracted three times with ethyl acetate (30 ml)
  9. washwashed three times with saline (30 ml)
  10. dry with materialThe organic layer is dried with sodium sulfate
  11. filtrationfiltered through a small amount of silica
  12. concentrationThe mixture is concentrated on a rotary evaporator
  13. customthe product is recrystallized from ethyl acetate/hexane

Quellen und Nachweise

ORD-Eintrag
ord-65e790c433c643c092da1e4c61ffd87b
Quelldatensatz
uspto-grants-2003_01
Patentnummer
US06509491B2

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