Reaction #2341

Reaction equation

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

Yield 19.6%

Solvents

dichloromethane

Conditions

Workup

1. 1
   Otherwas obtained
2. 2
   workup.STIRRINGthe mixture stirred for 4 hours
3. 3
   OtherThe solid which had precipitated during the reaction
4. 4
   Filtrationwas filtered off
5. 5
   OtherThe 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
   Otherthe aqueous layer separated
10. 10
    ExtractionThe precipitate was extracted twice into ethyl acetate
11. 11
    Filtrationthe combined extracts filtered through phase
12. 12
    Otherseparating paper
13. 13
    Otherevaporated
14. 14
    OtherThe residue was purified by flash chromatography on silica gel
15. 15
    Washeluting with methanol/dichloromethane/0.89 S

Procedure

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