تفاعل #5802

معادلة التفاعل

(±)-cis-6-(2-aminoethyl)-1,3-dioxane-4-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-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide

المردود 23.1%

المذيبات

dimethyl sulfoxide

water

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe solution is cooled
2. 2
   أخرىThe layers are separated
3. 3
   غسيلthe organic layer washed with water (2×50 mL) and 5% sodium hydroxide solution (2×100 mL
4. 4
   استخلاصto extract the intermediate acid from unreacted diketone)
5. 5
   استخلاصextracted with 30 mL of ethyl acetate
6. 6
   workup.ADDITIONA drop of concentrated hydrochloric acid is added to the ethyl acetate solution
7. 7
   تركيزThe solution is concentrated in vacuo
8. 8
   workup.DISSOLUTIONthe concentrate is redissolved in 30 mL of ethyl acetate
9. 9
   workup.ADDITIONtreated with one drop of concentrated hydrochloric acid
10. 10
    تركيزconcentrated in vacuo
11. 11
    workup.DISSOLUTIONdissolved in 6 mL of toluene
12. 12
    أخرىTrans-(±)-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 crystallizes
13. 13
    أخرىis isolated by filtration

الإجراء التجريبي

A solution of 0.26 g (1.21 mmol) of (±)-cis-6-(2-aminoethyl)-1,3-dioxane-4-acetic acid and 0.504 g (1.20 mmol) of (±)-4-fluoro-α-[2-methyl-1-oxopropyl]-γ-oxo-N,β-diphenylbenzenebutaneamide 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 (2×100 mL--to extract the intermediate acid from unreacted diketone). The aqueous layer is acidified with dilute hydrochloric acid solution 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-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide crystallizes and is isolated by filtration. A total of 0.15 g of 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.

المصدر