Reacción #2341

Ecuación de reacción

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

Rendimiento 19.6%

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas obtained
2. 2
   workup.STIRRINGthe mixture stirred for 4 hours
3. 3
   OtroThe solid which had precipitated during the reaction
4. 4
   Filtraciónwas filtered off
5. 5
   OtroThe filtrate was evaporated
6. 6
   workup.ADDITIONthe residue treated with ethyl acetate (20 ml)
7. 7
   Filtraciónfiltered
8. 8
   ExtracciónThe filtrate was extracted with 2N hydrochloric acid (2×10 ml)
9. 9
   Otrothe aqueous layer separated
10. 10
    ExtracciónThe precipitate was extracted twice into ethyl acetate
11. 11
    Filtraciónthe combined extracts filtered through phase
12. 12
    Otroseparating paper
13. 13
    Otroevaporated
14. 14
    OtroThe residue was purified by flash chromatography on silica gel
15. 15
    Lavadoeluting with methanol/dichloromethane/0.89 S

Procedimiento

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)+.

Fuente