反応 #11004

反応方程式

4-bromo-3-nitrobenzotrifluoride

triethylamine

methanol

sodium thiomethoxide

water

→

6a

Methyl 2-Methylthio-4-trifluoromethylbenzoate

反応条件

後処理

1. 1
   workup.ADDITIONwas added
2. 2
   その他purged with helium three times and carbon monoxide (CO) four times
3. 3
   温度was maintained between 50 and 75 psi
4. 4
   workup.ADDITIONby the addition of carbon monoxide as necessary
5. 5
   温度The mixture was cooled
6. 6
   workup.DISTILLATIONthe bulk of the solvent was distilled at reduced pressure
7. 7
   workup.ADDITIONWater (10 mL), toluene (15 mL) and 3 N HCl (10 mL) were added
8. 8
   ろ過the mixture was filtered
9. 9
   その他to remove fine particulates
10. 10
    その他The layers were separated
11. 11
    洗浄the organic layer was washed with aqueous sodium bicarbonate (10 mL)
12. 12
    その他immersed in a cool water bath
13. 13
    その他to consume >95% of 5a
14. 14
    workup.ADDITIONAqueous sodium bicarbonate (10 mL) was added to the reaction mixture
15. 15
    workup.ADDITIONthe layers were then thoroughly mixed
16. 16
    その他to separate
17. 17
    抽出The aqueous layer was extracted further with toluene (2×15 mL)
18. 18
    乾燥The combined organic solution was dried over Na2SO4
19. 19
    濃縮concentrated

実験手順

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.

出典