反应详情

To stirred suspension of 4-[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 azodicaboxylate (1.35 g). The mixture was stirred until complete solution was obtained. Methyl-4-hydroxy-3-vinylbutyrate (1.2 g) was added drowise 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. ammoniium 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)+.

1. stirringThe mixture was stirred until complete solution
2. customwas obtained
3. stirringthe mixture stirred for 4 hours
4. customThe solid which had precipitated during the reaction
5. filtrationwas filtered off
6. customThe filtrate was evaporated
7. additionthe residue treated with ethyl acetate (20 ml)
8. filtrationfiltered
9. extractionThe filtrate was extracted with 2N hydrochloric acid (2×10 ml)
10. customthe aqueous layer separated
11. extractionThe precipitate was extracted twice into ethyl acetate
12. filtrationthe combined extracts filtered through phase
13. customseparating paper
14. customevaporated
15. customThe residue was purified by flash chromatography on silica gel
16. washeluting with methanol/dichloromethane/0.89 S.G