Triethyl phosphonoacetate → (E)-(R)-4-tert-butoxycarbonylamino-6-(4-heptyloxy-phenyl)-4-methyl-hex-2-enoic acid ethyl ester

HRID 12591

Reaktionsgleichung

Reaktionsgleichung von HRID 12591
[CH2:1]([O:3][C:4](=[O:14])[CH2:5]P(OCC)(OCC)=O)[CH3:2].C([Li])CCC.[C:20]([O:24][C:25](=[O:47])[NH:26][C@:27]([CH:45]=O)([CH3:44])[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:32][CH:31]=1)([CH3:23])([CH3:22])[CH3:21].C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:14])/[CH:5]=[CH:45]/[C@@:27]([NH:26][C:25]([O:24][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:47])([CH3:44])[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:32][CH:31]=1)[CH3:2]

Komponenten

7

Edukt 4

HCID 13345Triethyl phosphonoacetateHCID 516892Sodium BicarbonateHCID 59339517[(R)-1-Formyl-3-(4-heptyloxy-phenyl)-1-methyl-propyl]-carbamic acid tert-butyl esterHCID 178418339Butyllithium

Produkt 1

HCID 58897683(E)-(R)-4-tert-butoxycarbonylamino-6-(4-heptyloxy-phenyl)-4-methyl-hex-2-enoic acid ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a stirred solution of (diethoxy-phosphoryl)-acetic acid ethyl ester (429 mg, 1.92 mMol) in dry THF (7 ml) is added n-butyllithium (0.66 ml, 2.5M in hexane, 1.66 mMol) at −78° C. The mixture was stirred at −78° C. for 1 hour. After that time, a solution of [(R)-1-formyl-3-(4-heptyloxy-phenyl)-1-methyl-propyl]-carbamic acid tert-butyl ester (500 mg, 1.28 mMol) in THF (4 ml) is added and stirring is continued at −78° C. for 1.5 hours. The mixture is allowed to warm to RT and then stirred at RT for 2 hours. The reaction mixture is then poured onto a biphasic mixture of AcOEt and NaHCO3 (saturated aqueous solution) and the aqueous phase is extracted twice with AcOEt. The combined organic layers are dried (Na2SO4) and concentrated under reduced pressure. Column chromatography eluting with 4% AcOEt in toluene gives the title compound as a colourless oil.

Aufarbeitung

  1. stirringstirring
  2. waitis continued at −78° C. for 1.5 hours
  3. temperatureto warm to RT
  4. stirringstirred at RT for 2 hours
  5. extractionthe aqueous phase is extracted twice with AcOEt
  6. dry with materialThe combined organic layers are dried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. washColumn chromatography eluting with 4% AcOEt in toluene

Quellen und Nachweise

ORD-Eintrag
ord-e219271ff5654914b84b2a1a70a9aa35
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07728020B2

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