Methanol → Methyl 2-(methylthio)-4-(trifluoromethyl)benzoate

Temperatur

100 °C

Dichlorobis(triphenylphosphine)palladium (140 mg; 0.20 mmol; 0.01 equiv) was added to a 100-mL autoclave. A mixture of 4-bromo-3-nitrobenzotrifluoride (4a; 3.06 mL; 20 mmol), triethylamine (3.5 mL; 25 mmol; 1.25 equiv), and methanol (60 mL; 75 equiv) was added and the mixture was pressurized and purged with helium three times and carbon monoxide (CO) four times. The reaction mixture was placed under 60 psi carbon monoxide and heated to 100° C. for 6 h. during which time the pressure was maintained between 50 and 75 psi by the addition of carbon monoxide as necessary. The mixture was cooled and vented and the bulk of the solvent was distilled at reduced pressure. Water (10 mL), toluene (15 mL) and 3 N HCl (10 mL) were added and the mixture was filtered to remove fine particulates. The layers were separated and the organic layer was washed with aqueous sodium bicarbonate (10 mL). The organic solution was then added to a mixture of sodium thiomethoxide (1.82 g; 26 mmol; 1.3 equiv) and tetrabutylammonium bromide (0.64 g; 2.0 mmol; 0.10 equiv) dissolved in water (6.85 mL) and immersed in a cool water bath. The reaction mixture was stirred overnight (18 h) at ambient temperature to consume >95% of 5a according to gas chromatography (GC) analysis. Aqueous sodium bicarbonate (10 mL) was added to the reaction mixture and the layers were then thoroughly mixed and allowed to separate. The aqueous layer was extracted further with toluene (2×15 mL). The combined organic solution was dried over Na2SO4 and concentrated to afford 3.71 g of 6a. The crude product was flash-chromatographed and eluted with 1:9 ethyl acetate:heptane to afford 2.71 g (54% overall from 4a) of 6a.

1. additionwas added
2. custompurged with helium three times and carbon monoxide (CO) four times
3. temperaturewas maintained between 50 and 75 psi
4. additionby the addition of carbon monoxide as necessary
5. temperatureThe mixture was cooled
6. distillationthe bulk of the solvent was distilled at reduced pressure
7. additionWater (10 mL), toluene (15 mL) and 3 N HCl (10 mL) were added
8. filtrationthe mixture was filtered
9. customto remove fine particulates
10. customThe layers were separated
11. washthe organic layer was washed with aqueous sodium bicarbonate (10 mL)
12. customimmersed in a cool water bath
13. customto consume >95% of 5a
14. additionAqueous sodium bicarbonate (10 mL) was added to the reaction mixture
15. additionthe layers were then thoroughly mixed
16. customto separate
17. extractionThe aqueous layer was extracted further with toluene (2×15 mL)
18. dry with materialThe combined organic solution was dried over Na2SO4
19. concentrationconcentrated

ORD-Eintrag

ord-d4ad2d2b18aa4c3b8db9e260bf88c5de

Quelldatensatz

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07094919B2