Reaktion #5793

Reaktionsgleichung

(±)-cis-9-(2-aminoethyl)-6,10-dioxaspiro[4.5]decane-7-acetic acid

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

diethyl ether

ammonium chloride

→

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

Ausbeute 24.7%

Lösungsmittel

dimethyl sulfoxide

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe solution is cooled
2. 2
   SonstigeThe layers are separated
3. 3
   Waschenthe organic layer washed with water (2×50 mL) and 5% sodium hydroxide solution (2×100mL
4. 4
   Extraktionto extract the intermediate protected acid from unreacted diketone)
5. 5
   Extraktionextracted with 30 mL of ethyl acetate
6. 6
   workup.ADDITIONA drop of concentrated hydrochloric acid is added to the ethyl acetate solution
7. 7
   workup.WAITto stand 18 hours
8. 8
   EinengenThe solution is concentrated in vacuo
9. 9
   workup.DISSOLUTIONthe concentrate is redissolved in 30 mL of ethyl acetate
10. 10
    workup.ADDITIONtreated with one drop of concentrated hydrochloric acid
11. 11
    workup.STIRRINGThe solution is stirred two hours
12. 12
    Einengenconcentrated in vacuo
13. 13
    workup.DISSOLUTIONdissolved in 6 mL of toluene
14. 14
    SonstigeTrans-(±)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo-2 H-pyran-2-yl)ethyl]-1 H-pyrrole-3-carboxamide crystallizes
15. 15
    Sonstigeis isolated by filtration

Vorschrift

A solution of 0.295 g (1.21 mmol) of (±)-cis-9-(2-aminoethyl)-6,10-dioxaspiro[4.5]decane-7-acetic acid and 0.504 g (1.20 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 5 mL of dimethyl sulfoxide is heated at 105° C. for 15 hours. The solution is cooled and poured into 100 mL of diethyl ether and 50 mL of saturated ammonium chloride in water. The layers are separated and the organic layer washed with water (2×50 mL) and 5% sodium hydroxide solution (2×100mL--to extract the intermediate protected acid from unreacted diketone). The aqueous layer is acidified with dilute hydrochloric acid solution, stirred for three hours and extracted with 30 mL of ethyl acetate. A drop of concentrated hydrochloric acid is added to the ethyl acetate solution and allowed to stand 18 hours. The solution is concentrated in vacuo and the concentrate is redissolved in 30 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 6 mL of toluene. Trans-(±)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo-2 H-pyran-2-yl)ethyl]-1 H-pyrrole-3-carboxamide crystallizes and is isolated by filtration. A total of 0.16 g of trans-(±)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo-2 H-pyran-2-yl)ethyl]-1 H-pyrrole-3-carboxamide is isolated in two crops.

Quelle