Reaction #56482

Reaction equation

mercaptoacetic acid

hydrochloric acid

Ethyl 4-(4-oxobutyl)benzoate

1-amino-3-(tetrahydro-2H-pyran-2-yloxy)octane

sodium sulfate

→

title compound

Yield 31.6%

Ethyl 4-{3-[3-(3-Hydroxyoctyl)-4-oxo-2-thiazolidinyl]propyl}benzoate

Yield 31.6%

Solvents

water

chloroform

methanol

Conditions

Workup

1. 1
   workup.STIRRINGstirred for 1 hour
2. 2
   OtherThe solid is subsequently removed by filtration
3. 3
   Washwashed with a small quantity of benzene
4. 4
   workup.ADDITIONThe combined filtrate and washings are diluted with benzene (70 ml.)
5. 5
   TemperatureThe resulting solution is refluxed in a Dean-Stark apparatus for 3 hours
6. 6
   Washwashed successively with dilute hydrochloric acid, 5% sodium bicarbonate
7. 7
   Dryingdried over anhydrous magnesium sulfate
8. 8
   Concentrationconcentrated
9. 9
   Otherto give an oil residue
10. 10
    workup.STIRRINGstirred at ambient temperature for 16 hours
11. 11
    Extractionfollowed by extraction with ether
12. 12
    ExtractionThe ethereal extract
13. 13
    Washis washed with water, 5% sodium bicarbonate
14. 14
    Dryingdried over anhydrous magnesium sulfate
15. 15
    Filtrationfiltered
16. 16
    OtherEvaporation of the filtrate in vacuo
17. 17
    Otherprovides an oil residue which
18. 18
    WashElution with chloroform-methanol (100:1; v:v; 1950 ml.)
19. 19
    Otherprovides impure material
20. 20
    Washfurther elution with the same eluant (450 ml.)

Procedure

Ethyl 4-(4-oxobutyl)benzoate (4.63 g., 21 mmol.) is added dropwise to 1-amino-3-(tetrahydro-2H-pyran-2-yloxy)octane (4.82 g., 21 mmol.) at ambient temperature. The resulting mixture is stirred for 15 minutes before adding anhydrous sodium sulfate (4 g.), and then stirred for 1 hour. The solid is subsequently removed by filtration and washed with a small quantity of benzene. The combined filtrate and washings are diluted with benzene (70 ml.) and then treated with mercaptoacetic acid (1.93 g., 21 mmol.). The resulting solution is refluxed in a Dean-Stark apparatus for 3 hours. The reaction mixture is allowed to cool to room temperature, washed successively with dilute hydrochloric acid, 5% sodium bicarbonate, dried over anhydrous magnesium sulfate, and concentrated to give an oil residue. A methanol solution (50 ml.) of the oil residue is treated with concentrated hydrochloric acid (0.2 ml.) and then stirred at ambient temperature for 16 hours. The reaction mixture is diluted with cold water, followed by extraction with ether. The ethereal extract is washed with water, 5% sodium bicarbonate, dried over anhydrous magnesium sulfate, and filtered. Evaporation of the filtrate in vacuo provides an oil residue which is then applied to a silica gel column (300 g.) with chloroform. Elution with chloroform-methanol (100:1; v:v; 1950 ml.) provides impure material; further elution with the same eluant (450 ml.) gives the title compound as a pale yellow oil (2.80 g., 6.64 mmol., 31%), pmr (CDCl3) δ0.90 (3H, t), 1.40 (3H, t), 3.53 (2H, s), 4.40 (2H, q), 4.70 (1H, m), 7.22 (2H, d), 8.0 (2H, d).

Source