Reaction #739966

Reaction equation

1-cyclooctyl-2-aminomethyl-pyrrolidine

2,4-dimethoxy-5-methyl sulphonyl benzoic acid

acetone

ethyl chloroformate

→

N-(1-cyclooctyl-2-pyrrolidinyl methyl)-2,4-dimethoxy-5-methyl-sulphonyl benzamide

Solvents

triethylamine

water

Conditions

Workup

1. 1
   Otherfitted with an agitator
2. 2
   TemperatureThe suspension is cooled to from 0° to +5° C.
3. 3
   Temperaturecooled to about 0° C.
4. 4
   workup.STIRRINGThe reaction medium is agitated at room temperature
5. 5
   workup.WAITthen left
6. 6
   OtherThe solvents are evaporated under vacuum
7. 7
   workup.DISSOLUTIONthe residue is dissolved in 100 ml of water
8. 8
   ExtractionThe organic phase is extracted 3 times with 50 ml of methylene chloride
9. 9
   Dryingdried over magnesium sulphate
10. 10
    Filtrationfiltered
11. 11
    Otherevaporated to dryness under vacuum
12. 12
    workup.DISSOLUTIONThe residue is dissolved in 100 ml of water
13. 13
    FiltrationThe solution is filtered in the presence of carbon black
14. 14
    OtherA gum is precipitated
15. 15
    ExtractionThis is extracted 3 times with 50 ml of methylene chloride
16. 16
    Washthe organic solution is washed twice with 50 ml of water
17. 17
    Dryingdried over magnesium sulphate
18. 18
    FiltrationIt is filtered
19. 19
    Otherthe solvent is evaporated under vacuum
20. 20
    Otherthe residue re-crystallised in 200 ml of isopropanol
21. 21
    FiltrationThe crystals are filtered off
22. 22
    Washwashed twice with a little iced isopropanol
23. 23
    Otherdried in an oven at 50° C.

Procedure

13 g of 2,4-dimethoxy-5-methyl sulphonyl benzoic acid, 150 ml of acetone, 28 ml of water and 7 ml of triethylamine (density 0.726) are placed in a 250 ml flask fitted with an agitator, a thermometer, a condenser and a dropping funnel. The suspension is cooled to from 0° to +5° C., then 5.4 g of ethyl chloroformate is added drop by drop. The mixture is agitated for 45 minutes at room temperature and cooled to about 0° C., then 13.8 g of 1-cyclooctyl-2-aminomethyl-pyrrolidine is added drop by drop. There is complete solubilisation. The reaction medium is agitated at room temperature then left to stand. The solvents are evaporated under vacuum and the residue is dissolved in 100 ml of water and 20 ml of hydrochloric acid (density 1.18). The organic phase is extracted 3 times with 50 ml of methylene chloride, dried over magnesium sulphate, filtered and evaporated to dryness under vacuum. The residue is dissolved in 100 ml of water. The solution is filtered in the presence of carbon black and the filtrate made alkaline with 10 ml of ammonia. A gum is precipitated. This is extracted 3 times with 50 ml of methylene chloride, and the organic solution is washed twice with 50 ml of water and dried over magnesium sulphate. It is filtered, then the solvent is evaporated under vacuum and the residue re-crystallised in 200 ml of isopropanol. The crystals are filtered off, washed twice with a little iced isopropanol and dried in an oven at 50° C.

Source