Réaction #56484

Équation de réaction

hydrochloric acid

sodium sulfate

HSCH2CO2H

Ethyl 4-(4-oxobutyl)benzoate

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

→

title compound

Rendement 32.0%

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

Rendement 32.0%

Solvants

methanol

carbon tetrachloride

chloroform

water

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGStirring
2. 2
   workup.WAITis continued for 2 hours
3. 3
   AutreThe solid is removed by filtration
4. 4
   Lavagewashed with a small quantity of benzene
5. 5
   workup.ADDITIONThe combined filtrate and washings are diluted with benzene (70 ml.)
6. 6
   Températurerefluxed in a Dean-Stark apparatus for 16 hours
7. 7
   Températureto cool to room temperature
8. 8
   Lavagesubsequently washed with diluted hydrochloric acid and 5% sodium bicarbonate
9. 9
   Séchagedried over anhydrous magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    AutreEvaporation in vacuo
12. 12
    Autreaffords an oil residue which
13. 13
    workup.STIRRINGThe resulting mixture is stirred at ambient temperature for 3 hours
14. 14
    Extractionextracted with ether
15. 15
    ExtractionThe ethereal extract
16. 16
    Lavageis washed with diluted sodium bicarbonate
17. 17
    Séchagedried over anhydrous magnesium sulfate
18. 18
    Filtrationfiltered
19. 19
    Concentrationconcentrated
20. 20
    Autreto give an oil residue
21. 21
    LavageElution with chloroform-methanol (100:1; v:v; 630 ml.)
22. 22
    Autregives impure material
23. 23
    LavageFurther elution with the same eluant (300 ml.)

Mode opératoire

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).

Source