Reaktion #56484

Reaktionsgleichung

hydrochloric acid

sodium sulfate

HSCH2CO2H

Ethyl 4-(4-oxobutyl)benzoate

1-amino-2-[1-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]ethane

→

title compound

Ausbeute 32.0%

4-{3-[3-[2-(1-Hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]propyl}benzoic Acid

Ausbeute 32.0%

Lösungsmittel

methanol

carbon tetrachloride

chloroform

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGStirring
2. 2
   workup.WAITis continued for 2 hours
3. 3
   SonstigeThe solid is removed by filtration
4. 4
   Waschenwashed with a small quantity of benzene
5. 5
   workup.ADDITIONThe combined filtrate and washings are diluted with benzene (70 ml.)
6. 6
   Temperaturrefluxed in a Dean-Stark apparatus for 16 hours
7. 7
   Temperaturto cool to room temperature
8. 8
   Waschensubsequently washed with diluted hydrochloric acid and 5% sodium bicarbonate
9. 9
   Trocknendried over anhydrous magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    SonstigeEvaporation in vacuo
12. 12
    Sonstigeaffords an oil residue which
13. 13
    workup.STIRRINGThe resulting mixture is stirred at ambient temperature for 3 hours
14. 14
    Extraktionextracted with ether
15. 15
    ExtraktionThe ethereal extract
16. 16
    Waschenis washed with diluted sodium bicarbonate
17. 17
    Trocknendried over anhydrous magnesium sulfate
18. 18
    Filtrationfiltered
19. 19
    Einengenconcentrated
20. 20
    Sonstigeto give an oil residue
21. 21
    WaschenElution with chloroform-methanol (100:1; v:v; 630 ml.)
22. 22
    Sonstigegives impure material
23. 23
    WaschenFurther elution with the same eluant (300 ml.)

Vorschrift

Ethyl 4-(4-oxobutyl)benzoate (4.15 g., 18.8 mmol.) is added dropwise to a stirred solution of 1-amino-2-[1-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]ethane in carbon tetrachloride (1 ml.) maintained at 25° C. The resulting mixture is stirred for 30 minutes before being treated with anhydrous sodium sulfate (4 g.). Stirring is continued for 2 hours. The solid is removed by filtration and washed with a small quantity of benzene. The combined filtrate and washings are diluted with benzene (70 ml.), treated with HSCH2CO2H (1.84 g., 20 mmole.) in one portion, and then refluxed in a Dean-Stark apparatus for 16 hours. The reaction mixture is allowed to cool to room temperature, subsequently washed with diluted hydrochloric acid and 5% sodium bicarbonate, dried over anhydrous magnesium sulfate, and filtered. Evaporation in vacuo affords an oil residue which is dissolved in methanol (50 ml.) plus concentrated hydrochloric acid (0.2 ml.). The resulting mixture is stirred at ambient temperature for 3 hours, diluted with water, and extracted with ether. The ethereal extract is washed with diluted sodium bicarbonate, dried over anhydrous magnesium sulfate, filtered, and concentrated to give an oil residue. The oil residue is then applied to a silica gel column (120 g.) with chloroform. Elution with chloroform-methanol (100:1; v:v; 630 ml.) gives impure material. Further elution with the same eluant (300 ml.) provides the title compound (2.5 g., 5.96 mmol., 32%) as a pale yellow oil, pmr (CDCl3) δ1.38 (3H, t), 3.50 (2H, s), 4.40 (2H, q), 4.72 (1H, m), 7.23 (2 H, d), 8.00 (2H, d).

Quelle