Реакция #2341

Уравнение реакции

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

Выход 19.6%

Растворители

dichloromethane

Условия реакции

Обработка

1. 1
   Другоеwas obtained
2. 2
   workup.STIRRINGthe mixture stirred for 4 hours
3. 3
   ДругоеThe solid which had precipitated during the reaction
4. 4
   Фильтрацияwas filtered off
5. 5
   ДругоеThe filtrate was evaporated
6. 6
   workup.ADDITIONthe residue treated with ethyl acetate (20 ml)
7. 7
   Фильтрацияfiltered
8. 8
   ЭкстракцияThe filtrate was extracted with 2N hydrochloric acid (2×10 ml)
9. 9
   Другоеthe aqueous layer separated
10. 10
    ЭкстракцияThe precipitate was extracted twice into ethyl acetate
11. 11
    Фильтрацияthe combined extracts filtered through phase
12. 12
    Другоеseparating paper
13. 13
    Другоеevaporated
14. 14
    ДругоеThe residue was purified by flash chromatography on silica gel
15. 15
    Промывкаeluting with methanol/dichloromethane/0.89 S

Методика

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)+.

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