4-Toluenesulfonyl chloride → 1-(3-(1-Pyrrolidinyl)propyl)-3-ethylcarbodiimide

Temperature

0 °C

To a solution of 31.0 g (0.156 mol) N-ethyl-N′-3-(1-pyrrolidinyl)propyl urea in 500 mL dichloromethane was added 62.6 g (0.62 mol) triethylamine and the solution was cooled to 0° C. To this solution were then added 59.17 g (0.31 mol) 4-toluenesulfonyl chloride in 400 mL dichloromethane dropwise at such a rate as to maintain the reaction at 0-5° C. After the addition was complete, the reaction mixture was warmed to room temperature and then heated to reflux for 4 hours. After cooling to room temperature, the reaction mixture was washed with saturated aqueous potassium carbonate (3×150 mL). The aqueous phases were combined and extracted with dichloromethane. All organic phases were combined and concentrated under reduced pressure. The resultant orange slurry was suspended in 250 mL diethyl ether and the solution decanted off from the solid. The slurry/decantation process was repeated 3 more times. The ether solutions were combined and concentrated under reduced pressure to give 18.9 g (67%) of the desired product as a crude orange oil. A portion of the oil was distilled under vacuum to give a colorless oil distilling at 78-82° C. (0.4 mm Hg).

1. temperatureto maintain
2. customthe reaction at 0-5° C
3. additionAfter the addition
4. temperaturethe reaction mixture was warmed to room temperature
5. temperatureheated
6. temperatureto reflux for 4 hours
7. temperatureAfter cooling to room temperature
8. washthe reaction mixture was washed with saturated aqueous potassium carbonate (3×150 mL)
9. extractionextracted with dichloromethane
10. concentrationconcentrated under reduced pressure
11. customthe solution decanted off from the solid
12. concentrationconcentrated under reduced pressure

ORD record

ord-19d5add7cb6f4eb1b61337ae3fad4547

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06667305B1