Tributyltin Chloride → 1-Methyl-4-((4-(tributylstannyl)furan-2-yl)methyl)piperazine

Temperature

-78 °C

A stirred mixture of 1-((4-bromofuran-2-yl)methyl)-4-methylpiperazine (2.10 g, 8.10 mmol) and THF (50 mL) was cooled to −78° C. in a dry ice/acetone bath. tert-Butyllithium (7.60 mL, 12.2 mmol; 1.6 M in pentane) was added and the reaction mixture was stirred for 30 minutes. Next, tributylchlorostannane (2.09 ml, 7.70 mmol) was added and the reaction mixture was stirred for 30 minutes. The reaction was quenched by addition of pH 7 phosphate buffer (20 mL) and warming to room temperature. The mixture was extracted with diethyl ether, dried over sodium sulfate, filtered and concentrated. The crude material was purified on a Biotage 40S column, eluting with 1:1 EtOAc/hexanes (500 mL), 2:1 EtOAc/hexanes (500 mL), then EtOAc (1 L) to provide a product mixture as a light yellow oil (0.77 g, 86:14 ratio of 1-((4-bromo-5-(tributylstannyl)furan-2-yl)methyl)-4-methylpiperazine to 1-methyl-4-((4-(tributylstannyl)furan-2-yl)methyl)piperazine by 1H-NMR). The mixture was carried forward without separation at this step.

1. stirringthe reaction mixture was stirred for 30 minutes
2. customThe reaction was quenched by addition of pH 7 phosphate buffer (20 mL)
3. temperaturewarming to room temperature
4. extractionThe mixture was extracted with diethyl ether
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude material was purified on a Biotage 40S column
9. washeluting with 1:1 EtOAc/hexanes (500 mL), 2:1 EtOAc/hexanes (500 mL)

ORD record

ord-14f4b5fc9e8a43ab8e4306a2a1df8cfc

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07723330B2