2,4-Dichloro-5-(trifluoromethyl)pyrimidine → 4-Chloro-2-(methylthio)-5-(trifluoromethyl)pyrimidine

To a solution of the 2,4-dichloro-5-(trifluoromethyl)pyrimidine (2.50 g, 11.5 mmol) in THF (50 mL) in an ice bath under nitrogen was added zinc(II) chloride (1.0 M in ether, 13.8 mL, 13.8 mmol) dropwise. The mixture was stirred in the ice bath for two hours, then sodium methanethiolate (0.888 g, 12.7 mmol) was added. The mixture was stirred overnight, allowing the reaction to slowly come to room temperature. After 18 hours the reaction was quenched with 2 M HCl (15 mL), and the organics removed by evaporation under reduced pressure. The aqueous residue was diluted with brine (15 mL), and extracted with DCM (3×30 mL). The combined organic phases were dried (phase separator) and carefully evaporated to give a pale yellow oil. Chromatography (Biotage Isolera, 2×40 g silica cartridge, 0-20% DCM/n-hexane) followed by carefully evaporation of solvent (40° C.@400 mmHg then room temperature@200 mmHg) gave the title compound (I13) (2.149 g, 82% yield) as a colourless oil; 1H NMR (600 MHz, CDCl3) δ 8.66 (s, 1H), 2.61 (s, 3H). LCMS Method C: rt: 7.95 min; m/z 229.1[M+H]+. Note: I13 is volatile.

1. customthe reaction
2. customto slowly come to room temperature
3. customAfter 18 hours the reaction was quenched with 2 M HCl (15 mL)
4. customthe organics removed by evaporation under reduced pressure
5. additionThe aqueous residue was diluted with brine (15 mL)
6. extractionextracted with DCM (3×30 mL)
7. customThe combined organic phases were dried (phase separator)
8. customcarefully evaporated
9. customto give a pale yellow oil
10. customChromatography (Biotage Isolera, 2×40 g silica cartridge, 0-20% DCM/n-hexane) followed by carefully evaporation of solvent (40° C.@400 mmHg

ORD 기록

ord-edbfc1abd4c74686bd3c8b3bfb537b67

출처 데이터셋

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09421205B2