Reaktion #87467

Reaktionsgleichung

aluminum

tetrahydrofuran

(2R,3S,4S)-2,3,4-tris-benzyloxy-5-hydroxy-6-(4-methoxy-benzyloxy)-5-(4-methoxy-benzyloxymethyl)-hexanoic acid methoxy-methyl-amide

tetrahydrofuran

n-Butyl lithium

oxygen

4-bromo-1-chloro-2-(4-ethoxy-benzyl)-benzene

→

(4S,5S)-3,4,5-tris-benzyloxy-2-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-6,6-bis-(4-methoxy-benzyloxymethyl)-tetrahydro-pyran-2-ol

Ausbeute 38.0%

Lösungsmittel

Diethyl ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigedried Biotage™ microwave vial 10-20 mL
2. 2
   Sonstigesealed with its
3. 3
   Sonstigecap
4. 4
   Sonstigeat −78° C.
5. 5
   workup.STIRRINGthe resulting mixture was stirred at −78° C. for 1 hour
6. 6
   Temperaturto maintain cold temperature
7. 7
   Sonstigethe reaction was quenched by dropwise addition of aqueous 1M hydrochloric acid solution
8. 8
   workup.STIRRINGThe resulting biphasic mixture was stirred at room temperature for 15 minutes
9. 9
   SonstigeThe organic phase was separated
10. 10
    Waschenwashed with brine
11. 11
    Trocknendried over magnesium sulfate
12. 12
    Filtrationfiltered
13. 13
    Einengenconcentrated
14. 14
    SonstigeChromatography over silica gel using a gradient of 10 to 40% ethyl acetate in heptane gave the product
15. 15
    workup.ADDITIONas a mixture of isomers (280 mg, 38% yield)

Vorschrift

n-Butyl lithium (1.0 mL, 2.5 M/hexanes, 3.25 equivalents) was added dropwise (1 drop every 5 seconds) to an oxygen degassed solution (placed in a pre dried Biotage™ microwave vial 10-20 mL sealed with its cap and placed under a positive stream of nitrogen gas) of 4-bromo-1-chloro-2-(4-ethoxy-benzyl)-benzene (815 mg, 3.25 equivalents) in anhydrous tetrahydrofuran (2.9 mL) at −78° C. and the resulting solution was stirred at this temperature for an additional hour. A solution of (2R,3S,4S)-2,3,4-tris-benzyloxy-5-hydroxy-6-(4-methoxy-benzyloxy)-5-(4-methoxy-benzyloxymethyl)-hexanoic acid methoxy-methyl-amide (I-1g) (600 mg) in anhydrous tetrahydrofuran (1.45 mL) was then added dropwise over 1.3 hours using a syringe pump and the resulting mixture was stirred at −78° C. for 1 hour before being allowed to warm to −25° C. over 14 hours (put in a deep Dewar covered with aluminum foil to maintain cold temperature; size of Dewar: external diameter 10 cm, internal diameter 8 cm, height 9 cm). Diethyl ether was added and the reaction was quenched by dropwise addition of aqueous 1M hydrochloric acid solution. The resulting biphasic mixture was stirred at room temperature for 15 minutes. The organic phase was separated, washed with brine, dried over magnesium sulfate, filtered and concentrated. Chromatography over silica gel using a gradient of 10 to 40% ethyl acetate in heptane gave the product as a mixture of isomers (280 mg, 38% yield).

Quelle