Triethylamine → N,N-dimethyl-1-[(2S)-pyrrolidin-2-yl]methanamine

Temperature

-78 °C

While cooling at −78° C., a solution of sulfuryl chloride (0.409 mL) in methylene chloride (30 mL) was added dropwise to a solution of (2S)-2-pyrrolidinemethanol (0.498 mL) and triethylamine (1.39 mL) in methylene chloride (30 mL) over a period of 10 minutes. The temperature of the resultant mixture was gradually returned to room temperature, followed by stirring of the mixture for 20 hours. The reaction mixture was partitioned between 1N aqueous hydrochloric acid and methylene chloride, and the organic layer was washed with saturated brine, followed by drying over sodium sulfate anhydrate. After filtration, the solvent was removed under reduced pressure, and a solution of 2.0M dimethylamine in tetrahydrofuran (25 mL) was added to the residue, followed by stirring in a sealed tube at an external temperature of. 100° C. for 14 hours and 30 minutes, and then cooled in air. Trifluoroacetic acid (one droplet) was added thereto. The resultant mixture was further stirred in a sealed tube at an external temperature of 100° C. for 21 hours and then cooled in air. The solvent was removed at normal pressure, and 2N aqueous sodium hydroxide (50 mL) was added to the residue, followed by stirring at 100° C. for 15 hours. The resultant mixture was cooled in air. Diethyl ether was added thereto for partitioning the mixture, and the organic layer was dried over sodium sulfate anhydrate. After filtration, the solvent was removed at normal pressure, to thereby give (2S)-2-dimethylaminomethylpyrrolidine.

1. customwas gradually returned to room temperature
2. customThe reaction mixture was partitioned between 1N aqueous hydrochloric acid and methylene chloride
3. washthe organic layer was washed with saturated brine
4. dry with materialby drying over sodium sulfate anhydrate
5. filtrationAfter filtration
6. customthe solvent was removed under reduced pressure
7. additiona solution of 2.0M dimethylamine in tetrahydrofuran (25 mL) was added to the residue
8. stirringby stirring in a sealed tube at an external temperature of
9. wait100° C. for 14 hours
10. temperature30 minutes, and then cooled in air
11. additionTrifluoroacetic acid (one droplet) was added
12. stirringThe resultant mixture was further stirred in a sealed tube at an external temperature of 100° C. for 21 hours
13. temperaturecooled in air
14. customThe solvent was removed at normal pressure, and 2N aqueous sodium hydroxide (50 mL)
15. additionwas added to the residue
16. stirringby stirring at 100° C. for 15 hours
17. temperatureThe resultant mixture was cooled in air
18. additionDiethyl ether was added
19. customfor partitioning the mixture
20. dry with materialthe organic layer was dried over sodium sulfate anhydrate
21. filtrationAfter filtration
22. customthe solvent was removed at normal pressure

ORD record

ord-17114150490d482dbb4f7138dd1d134d

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622471B2