2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 2-(2-(4-Fluoro-benzyl)-5-(5-chloro-2-(methylthio)pyrimidin-4-yl)thiophen-3-yl)ethanol

Temperatur

-78 °C

n-Butyllithium (5.4 mL, 1.6 M in hexanes, 8.63 mmol) was added dropwise to a solution of 2-(2-(4-fluorobenzyl)thiophen-3-yl)ethanol (0.97 g, 4.11 mmol) in anhydrous tetrahydrofuran (15 mL) at −78° C. The resulting mixture was stirred at −78° C. for 1 h and then a solution of 5-chloro-2-(methylthio)pyrimidine (0.79 g, 4.93 mmol) in 1 mL of tetrahydrofuran was added slowly. The mixture was stirred at −78° C. for 1 h and then at −40° C. for 2 h. The reaction was quenched with a solution (1.1 mL) of acetic acid and methanol (1:1) at −40° C. and then a solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.1.1 g, 4.93 mmol) in tetrahydrofuran (1 mL) was added. After complete addition the reaction was stirred at −40° C. for 1 h, then warmed to rt. 10 mL of aqueous sodium hydroxide (2 M) and 50 mL of water were added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (80 mL), dried over anhydrous sodium sulfate and filtered. The solvent was evaporated in vacuo and the product purified by flash chromatography eluting with ethyl acetate/hexane (1:4) to afford the title compound (0.45 g, 28%). MS (M+H)+ 395/397.

1. stirringThe mixture was stirred at −78° C. for 1 h
2. waitat −40° C. for 2 h
3. customThe reaction was quenched with a solution (1.1 mL) of acetic acid and methanol (1:1) at −40° C.
4. additionAfter complete addition the reaction
5. stirringwas stirred at −40° C. for 1 h
6. temperaturewarmed to rt
7. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
8. washThe combined organic layers were washed with brine (80 mL)
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. customThe solvent was evaporated in vacuo
12. customthe product purified by flash chromatography
13. washeluting with ethyl acetate/hexane (1:4)

ORD-Eintrag

ord-01b52c9df02548bca13060d153729ded

Quelldatensatz

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07786132B2