Réaction #2341

Équation de réaction

diethyl azodicarboxylate

Methyl-4-hydroxy-3-vinylbutyrate

4-[4-(4-pyridyl)piperazin-1-yl]phenol

triphenylphosphine

→

ammonium hydroxide

methyl 4-[4-[4-(4-pyridyl)piperazin-1-yl]-phenoxy]-3-vinylbutyrate

Rendement 19.6%

Solvants

dichloromethane

Conditions de réaction

Traitement

1. 1
   Autrewas obtained
2. 2
   workup.STIRRINGthe mixture stirred for 4 hours
3. 3
   AutreThe solid which had precipitated during the reaction
4. 4
   Filtrationwas filtered off
5. 5
   AutreThe filtrate was evaporated
6. 6
   workup.ADDITIONthe residue treated with ethyl acetate (20 ml)
7. 7
   Filtrationfiltered
8. 8
   ExtractionThe filtrate was extracted with 2N hydrochloric acid (2×10 ml)
9. 9
   Autrethe aqueous layer separated
10. 10
    ExtractionThe precipitate was extracted twice into ethyl acetate
11. 11
    Filtrationthe combined extracts filtered through phase
12. 12
    Autreseparating paper
13. 13
    Autreevaporated
14. 14
    AutreThe residue was purified by flash chromatography on silica gel
15. 15
    Lavageeluting with methanol/dichloromethane/0.89 S

Mode opératoire

To a stirred suspension of 4-[4-(4-pyridyl)piperazin-1-yl]phenol (1.98 g) in dichloromethane (30 ml) at 15° C. was added triphenylphosphine (2.04 g) followed by dropwise addition of diethyl azodicarboxylate (1.35 g). The mixture was stirred until complete solution was obtained. Methyl-4-hydroxy-3-vinylbutyrate (1.12 g) was added dropwise and the mixture stirred for 4 hours. The solid which had precipitated during the reaction was the starting phenol and was filtered off. The filtrate was evaporated and the residue treated with ethyl acetate (20 ml) and filtered. The filtrate was extracted with 2N hydrochloric acid (2×10 ml) and the aqueous layer separated and basified with 0.89 S.G. ammonium hydroxide. The precipitate was extracted twice into ethyl acetate and the combined extracts filtered through phase separating paper and evaporated. The residue was purified by flash chromatography on silica gel, eluting with methanol/dichloromethane/0.89 S. G. ammonium hydroxide v:v:v 7.5/92.5/0.75 to give RS methyl 4-[4-[4-(4-pyridyl)piperazin-1-yl]-phenoxy]-3-vinylbutyrate (0.29 g); NMR(CDCl3) δ 8.3(2H,d), 6.88(4H,m), 6.70(2H,d), 5.85(1H,m), 5.20(2H,m), 3.90(2H,m), 3.67(3H,s), 3.48(2H,m), 3.18(2H,m), 3.06(1H,m), 2.68(1H,m), 2.47(1H,m), 1.80(1H,br); m/e 382 (M+H)+.

Source