4,6-Dichloropyrimidine → 4-Chloro-6-(methylsulfanyl)pyrimidine

A mixture of 4,6-dichloro-pyrimidine 1 (20.93 g, 140 mmol), sodium thiomethoxide (10.34 g, 147 mmol) in THF (100 mL) is stirred at room temperature overnight. The reaction mixture is concentrated and the residue partitioned between ethyl acetate and brine. The organic layer is separated and washed with brine, dried over Na2SO4. The crude product is purified by recrystallization from hexanes (60 mL) to afford 4-chloro-6-methylsulfanyl-pyrimidine. The mother liquor is concentrated and the residue is purified by silica gel flash chromatography eluting with ethyl acetate in hexanes from 0% to 10% to give 4-chloro-6-methylsulfanyl-pyrimidine containing small amounts of byproduct 4,6-bis methylthio-pyrimidine, which is easily removed in the next step. 1H NMR 400 MHz (CDCl3) δ 8.72 (s, 1H), 7.21 (s, 1H), 2.58 (s, 3H).

1. concentrationThe reaction mixture is concentrated
2. customthe residue partitioned between ethyl acetate and brine
3. customThe organic layer is separated
4. washwashed with brine
5. dry with materialdried over Na2SO4
6. customThe crude product is purified by recrystallization from hexanes (60 mL)

ORD record

ord-518d3615083a4cdb9b912416df04b39b

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08026243B2