Water → (5s)-5-(Acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5h-dibenzo[a,c]cyclohepten-3-yl hydrogen methylphosphonate

HRID 720959

Reaktionsgleichung

Reaktionsgleichung von HRID 720959
[CH3:1][C:2]([NH:4][CH:5]1[C:15]2[CH:16]=[C:17]([OH:20])[CH:18]=[CH:19][C:14]=2[C:13]2[C:8](=[CH:9][C:10]([O:25][CH3:26])=[C:11]([O:23][CH3:24])[C:12]=2[O:21][CH3:22])[CH2:7][CH2:6]1)=[O:3].[CH3:27][P:28](Cl)(Cl)=[O:29].[OH2:32]>C1COCC1>[CH3:27][P:28](=[O:29])([OH:32])[O:20][C:17]1[CH:18]=[CH:19][C:14]2[C:13]3[C:12]([O:21][CH3:22])=[C:11]([O:23][CH3:24])[C:10]([O:25][CH3:26])=[CH:9][C:8]=3[CH2:7][CH2:6][C@H:5]([NH:4][C:2](=[O:3])[CH3:1])[C:15]=2[CH:16]=1

Komponenten

5

Edukt 3

HCID 962WaterHCID 12671Methyl phosphonic dichlorideHCID 97865N-Acetylcolchicinol

Produkt 1

HCID 57252105(5s)-5-(Acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5h-dibenzo[a,c]cyclohepten-3-yl hydrogen methylphosphonateAusbeute 41 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel4×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of N-acetyl-colchicinol (0.36 g; 1.0 mmol) in THF (40 ml) under argon was cooled to 0° C. and treated with a 1.0M solution of lithiumHMDS in THF (1.1 ml; 1.1 mmol). The mixture was stirred at 0° C. for 1 hour and then added in portions over about 2 hours to a solution of methylphosphonic dichloride (0.53 mg; 4.0 mmol) in THF (150 ml). The mixture was stirred at ambient temperature for 15 minutes. After addition of water (200 ml) the THF was removed by evaporation. After removal of the insoluble material by filtration, the filtrate was purified on HP20 SS resin eluting with a gradient of 0–60% methanol/water. The methanol was removed by evaporation and the mixture was adjusted to pH7.14 with sodium hydroxide (0.1 M). The appropriate fractions were freeze-dried to give (5S)-5-(acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl hydrogen methylphosphonate as a beige solid (180 mg).

Aufarbeitung

  1. stirringThe mixture was stirred at ambient temperature for 15 minutes
  2. customwas removed by evaporation
  3. customAfter removal of the insoluble material
  4. filtrationby filtration
  5. customthe filtrate was purified on HP20 SS resin
  6. washeluting with a gradient of 0–60% methanol/water
  7. customThe methanol was removed by evaporation
  8. customThe appropriate fractions were freeze-dried

Quellen und Nachweise

ORD-Eintrag
ord-de37eb0acdf1431ebb324dd7a7236732
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07135502B1

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