2-Chloro-5-(chloromethyl)pyridine → 2-Chloro-5-[(methylthio)methyl]pyridine

A solution of 5-chloromethyl-2-chloropyridine (8.1 g, 50 mmol) in ethanol (50 mL) was added to a suspension of sodium thiomethoxide solid (4.2 g, 60 mmol) in 100 mL ethanol under stirring. An exothermic reaction was observed during the addition and the mixture was then stirred at room temperature overnight. The solvent ethanol was removed under reduced pressure and the residue was re-dissolved in ether-EtOAc solvent and mixed with brine. The two phases were separated and the organic layer was dried over anhydrous Na2SO4, filtered, concentrated and purified by eluting through a silica gel plug with 40% EtOAc in hexane to give 8.14 g of 2-chloro-5-[(methylthio)methyl]pyridine (A) as a colorless oil in 94% yield. The product was analytically pure and directly used for the next step reaction. 1H NMR (300 MHz, CDCl3) δ 8.28 (dd, 1H), 7.65 (dd, 1H), 7.30 (d, 1H), 3.63 (s, 2H), 2.00 (s, 3H).

1. customAn exothermic reaction
2. additionwas observed during the addition
3. stirringthe mixture was then stirred at room temperature overnight
4. customThe solvent ethanol was removed under reduced pressure
5. dissolutionthe residue was re-dissolved in ether-EtOAc solvent
6. additionmixed with brine
7. customThe two phases were separated
8. dry with materialthe organic layer was dried over anhydrous Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. custompurified
12. washby eluting through a silica gel plug with 40% EtOAc in hexane

ORD record

ord-9e4079a88de8459cb462ed8d94158831

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08017788B2