Ethyl Acetate → 4-(4-Bromo-phenylsulfanylmethyl)pyridine

Temperature

2.5 °C

A suspension of 4-bromomethylpyridine hydrochloride (1.59 g, 6.3 mmol) in THF (10 mL) was treated dropwise with a solution of potassium carbonate (3.33 g, 24.0 mmol) in H2O (6 mL) at 0-5° C., and the resulting mixture was stirred at 0-5° C. for 10 min before being treated dropwise with a solution of 4-bromo-benzenethiol (1.14 g, 6.0 mmol) in THF (5.0 mL) at 0-5° C. under N2. The resulting reaction mixture was subsequently stirred at 0-5° C. for an additional 20 min. When TLC and LCMS showed that the reaction was complete, the reaction mixture was treated with water (15 mL) and ethyl acetate (25 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with water (2×15 mL) and saturated aqueous NaCl solution (10 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by flash column chromatography (5-25% EtOAc-hexane gradient elution) to afford the desired 4-(4-bromo-phenylsulfanylmethyl)pyridine 301 (1.374 g; 82%) as a pale-yellow solid, which was directly used in subsequent reactions.

1. customThe resulting reaction mixture
2. stirringwas subsequently stirred at 0-5° C. for an additional 20 min
3. customThe two layers were separated
4. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
5. washThe combined organic extracts were washed with water (2×15 mL) and saturated aqueous NaCl solution (10 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash column chromatography (5-25% EtOAc-hexane gradient elution)

ORD record

ord-94acfbbb23e04e139d30fa8a862d4b32

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07705026B2