Piperazine → 1-(Thiazol-2-yl)piperazine

Piperazine (3.44 g, 40 mmol) was added to a solution of 2-bromothiazole (1.8 ml, 20 mmol) in acetonitrile (90 ml). The mixture was heated at reflux for 20 h. The reaction was cooled down at RT and the precipitate (disubstituted piperazine) was filtered off. The filtrate was evaporated, the residue was partitioned between water and ethyl acetate, the organic phase was separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were extracted with HCl (1 M). The organic phase was discarded, and the aqueous layer was neutralized by addition of NaHCO3 (solid) to pH 8, and then extracted with EtOAc. The organic extracted was dried over sodium sulfate and evaporated, providing 1-thiazol-2-ylpiperazine (intermediate IIIa, 860 mg, 25% yield) as colorless oil. H-NMR (CDCl3): 2.98 (m, 4H), 3.48 (m, 4H), 6.56 (d, 1H, J=3.63 Hz), 7.20 (d, 1H, J=3.63 Hz).

1. temperatureThe mixture was heated
2. temperatureat reflux for 20 h
3. filtrationthe precipitate (disubstituted piperazine) was filtered off
4. customThe filtrate was evaporated
5. customthe residue was partitioned between water and ethyl acetate
6. customthe organic phase was separated
7. extractionthe aqueous layer was extracted twice with EtOAc
8. extractionThe combined organic layers were extracted with HCl (1 M)
9. additionthe aqueous layer was neutralized by addition of NaHCO3 (solid) to pH 8
10. extractionextracted with EtOAc
11. extractionThe organic extracted
12. dry with materialwas dried over sodium sulfate
13. customevaporated

ORD record

ord-0bcc925487dd4b4082cd3766fdfe4c9c

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07491821B2