反応 #51664

反応方程式

triethyl amine

t-butyl hypochlorite

1,1-dimethoxy-2-methylsulfanyl-ethane

2-chloro-4-fluoroaniline

→

7-chloro-5-fluoro-3-methylsulfanyl-1H-indole

収率 46.2%

溶媒

Water

methylene chloride

methylene chloride

methylene chloride

methylene chloride

反応条件

後処理

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   workup.ADDITIONwas added slowly
3. 3
   workup.ADDITIONwas added
4. 4
   その他to rise to room temperature
5. 5
   その他the organic layer was separated
6. 6
   乾燥dried over magnesium sulfate
7. 7
   ろ過filtered
8. 8
   その他evaporated to dryness
9. 9
   workup.ADDITIONcontaining triethylamine (2 ml)
10. 10
    温度refluxed overnight
11. 11
    その他The solvent was removed
12. 12
    その他The ether layer was then separated
13. 13
    洗浄washed with bicarbonate solution
14. 14
    乾燥dried over magnesium sulfate
15. 15
    ろ過filtered
16. 16
    その他evaporated to dryness
17. 17
    その他Purification by chromatography on silica gel (1:9 ethyl acetate:hexane)

実験手順

Following the procedure described in J.Amer.Chem.Soc. 96 (17), 5495 (1974) 2-chloro-4-fluoroaniline (1.45 g, 10 mmole) was dissolved in methylene chloride (35 ml) and stirred vigorously at −65° C. under nitrogen while freshly prepared t-butyl hypochlorite (1.08 g, 10 mmole) dissolved in 10 ml methylene chloride was added dropwise. Ten minutes after the completion of the addition a solution of 1,1-dimethoxy-2-methylsulfanyl-ethane (1.36 g, 10 mmole) dissolved in 10 ml methylene chloride was added slowly. The reaction mixture was stirred at −65° C. for 1 h after which time, triethyl amine (1.01 g, 10 mmole) dissolved in 10 ml methylene chloride was added and the temperature was allowed to rise to room temperature. Water was added and the organic layer was separated, dried over magnesium sulfate, filtered and evaporated to dryness. The oily residue was taken up in carbon tetrachloride (35 ml) containing triethylamine (2 ml) and refluxed overnight. The solvent was removed and replaced with ether (35 ml) and stirred in a two-phase system with 12 ml of 2N HCl for about 3 h. The ether layer was then separated, washed with bicarbonate solution, dried over magnesium sulfate, filtered and evaporated to dryness. Purification by chromatography on silica gel (1:9 ethyl acetate:hexane) afforded the pure 7-chloro-5-fluoro-3-methylsulfanyl-1H-indole (0.997 g, 46% yield).

出典