Réaction #84055

Équation de réaction

Serotonin hydrochloride

Ethylchloroformate

prostaglandin F2α

triethylamine

→

(Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-((E)-(S)-3-hydroxy-oct-1-enyl)-cyclopentyl]-hept-5-enoic acid [2-(5-hydroxy-1H-indol-3-yl)-ethyl]-amide

Rendement 68.0%

Solvants

ethyl acetate

CH2Cl2

Conditions de réaction

Traitement

1. 1
   Températurewas warmed to room temperature
2. 2
   workup.STIRRINGstirred for 16 hours
3. 3
   Lavagewashed with HCl (1 N), saturated sodium bicarbonate, and brine
4. 4
   SéchageThe organic portion was dried (MgSO4)
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated in vacuo
7. 7
   workup.ADDITIONThe residue was diluted with methanol and pyridinium p-toluenesulfonate (PPTs) (100 mg)
8. 8
   workup.ADDITIONwas added
9. 9
   workup.STIRRINGthe solution was stirred for 24 hours
10. 10
    AutreThe solvent was then removed in vacuo
11. 11
    workup.ADDITIONthe residue was diluted with ethyl acetate
12. 12
    Lavagewashed with HCl (1 N), saturated sodium bicarbonate, and brine
13. 13
    SéchageThe organic portion was dried (MgSO4)
14. 14
    Filtrationfiltered
15. 15
    Concentrationconcentrated in vacuo

Mode opératoire

A solution of the protected prostaglandin F2α (500 mg, 0.825 mmol) in CH2Cl2 (4.5 mL) was treated with triethylamine (290 μL, 2.06 mmol) with stirring and cooled to 0° C. Ethylchloroformate (87 μL, 0.907 mmol) was then added and after 15 minutes the reaction was warmed to room temperature. Serotonin hydrochloride (211 mg, 0.99 mmol) was added and stirred for 16 hours. The reaction was then diluted with ethyl acetate and washed with HCl (1 N), saturated sodium bicarbonate, and brine. The organic portion was dried (MgSO4), filtered and concentrated in vacuo. The residue was diluted with methanol and pyridinium p-toluenesulfonate (PPTs) (100 mg) was added and the solution was stirred for 24 hours. The solvent was then removed in vacuo, and the residue was diluted with ethyl acetate and washed with HCl (1 N), saturated sodium bicarbonate, and brine. The organic portion was dried (MgSO4), filtered and concentrated in vacuo. Flash column chromatography (silica gel, 19:1 ethyl acetate:methanol) gave (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-((E)-(S)-3-hydroxy-oct-1-enyl)-cyclopentyl]-hept-5-enoic acid [2-(5-hydroxy-1H-indol-3-yl)-ethyl]-amide (Compound 3) (287 mg, 68%).

Source