Ammonia → 1-Methyl-4-[(2S)-pyrrolidin-2-ylmethyl]piperazine

To a flame dried 3 neck 250 mL round bottom flask fitted with dry ice condenser, ammonia (50 mL) was condensed at −78° C. using an acetone bath. 1-Methyl-4-({(2S)-1-[(4-methylphenyl)sulfonyl]pyrrolidin-2-yl}methyl)piperazine (2.562 g, 7.790 mmol) dissolved in THF (40 mL), EtOH (2 mL) and NH3 (40 mL) was transferred via syringe into the reaction vessel. Lithium (0.500 g, 72.000 mmol) was added by small pieces into the stirred solution. Acetone bath was then removed and the reaction was allowed to reflux for 2 hours and then warmed up to rt. The reaction was quenched with H2O (50 mL) basified to pH 11 with ammonium hydroxide and extracted with EtOAc (3×). The aqueous layer was re-extracted with CH2Cl2/MeOH (90/10) and the combined organic extracts were dried over Na2SO4, filtered and concentrated to give the title compound as a yellow oil (1.300 g, 93% ). NMR (400 Mz, DMSO-d6): consistent. Reference: (Tetrahedron, 43(14), 3289, 1987).

1. customTo a flame dried 3 neck 250 mL round bottom flask
2. customfitted with dry ice condenser
3. customcondensed at −78° C.
4. customAcetone bath was then removed
5. temperatureto reflux for 2 hours
6. customThe reaction was quenched with H2O (50 mL)
7. extractionextracted with EtOAc (3×)
8. extractionThe aqueous layer was re-extracted with CH2Cl2/MeOH (90/10)
9. dry with materialthe combined organic extracts were dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-d8b1962b185f4a3f88cdd9be66c2571c

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07256198B2