Reaktion #5804

Reaktionsgleichung

(±)-cis-1,1-dimethylethyl 6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate

(±)-4-fluoro-α-[2-methyl-1-oxopropyl]-γ-oxo-N,β-diphenylbenzenebutaneamide

tetrahydrofuran

ammonium chloride

→

Trans-(±)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide

Lösungsmittel

heptane toluene

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturis heated
2. 2
   Temperaturat reflux for 24 hours
3. 3
   TemperaturThe solution is cooled
4. 4
   SonstigeThe layers are separated
5. 5
   Waschenthe organic layer washed with brine
6. 6
   workup.ADDITIONTo the organic layer is added 5 mL of 10% hydrochloric acid solution
7. 7
   workup.ADDITIONTo this solution is added 1.2 g of sodium hydroxide
8. 8
   workup.STIRRINGthe mixture is stirred for 30 hours
9. 9
   workup.ADDITIONby adding 50 mL of water, 30 mL of hexane
10. 10
    Sonstigeseparating the layers
11. 11
    workup.STIRRINGstirred for three hours
12. 12
    Extraktionextracted with 50 mL of ethyl acetate
13. 13
    workup.ADDITIONA drop of concentrated hydrochloric acid is added to the ethyl acetate solution
14. 14
    workup.WAITto stand 18 hours
15. 15
    EinengenThe solution is concentrated in vacuo
16. 16
    workup.DISSOLUTIONthe concentrate is redissolved in 50 mL of ethyl acetate
17. 17
    workup.ADDITIONtreated with one drop of concentrated hydrochloric acid
18. 18
    workup.STIRRINGThe solution is stirred two hours
19. 19
    Einengenconcentrated in vacuo
20. 20
    workup.DISSOLUTIONdissolved in 10 mL of toluene

Vorschrift

A solution of 0.79 g (2.89 mmol) of (±)-cis-1,1-dimethylethyl 6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate and 100 g (2.41 mmol) of (±)-4-fluoro-α-[2-methyl-1-oxopropyl]-γ-oxo-N,β-diphenylbenzenebutaneamide mixture of [R-(R*,R*)], [R-(R*,S*)], [S-(R*,R*)] and [S-(R*,S*)] isomers in 15 mL of heptane:toluene (9:1) is heated at reflux for 24 hours. The solution is cooled and poured into 100 mL of tetrahydrofuran and 50 mL of saturated ammonium chloride in water. The layers are separated and the organic layer washed with brine. To the organic layer is added 5 mL of 10% hydrochloric acid solution and the solution is stirred for 15 hours. To this solution is added 1.2 g of sodium hydroxide and the mixture is stirred for 30 hours. The reaction is stopped by adding 50 mL of water, 30 mL of hexane, and separating the layers. The aqueous layer is acidified with dilute hydrochloric acid solution, stirred for three hours and extracted with 50 mL of ethyl acetate. A drop of concentrated hydrochloric acid is added to the ethyl acetate solution and the solution is allowed to stand 18 hours. The solution is concentrated in vacuo and the concentrate is redissolved in 50 mL of ethyl acetate and treated with one drop of concentrated hydrochloric acid. The solution is stirred two hours, concentrated in vacuo, and dissolved in 10 mL of toluene. Trans-(±)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide is isolated in two crops.

Quelle