反应 #70809

反应方程式

methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylate

1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate

nitroethane

→

methyl 6-bromo-3-fluoro-1-isopropyl-1H-indole-4-carboxylate

收率 20.7%

反应条件

后处理

1. 1
   其他followed with a magnetic stir bar
2. 2
   其他The vial was capped
3. 3
   其他Reaction progress
4. 4
   其他After reaction completion the reaction solvent
5. 5
   其他was removed in-vacuo
6. 6
   workup.DISSOLUTIONThe residue was dissolved with DCM (1.4 ml)
7. 7
   workup.ADDITIONThe DCM solution was charged onto an analogix Si35 SF10-8 gram column
8. 8
   洗涤The compound was eluted with EtOAc/Hexanes, 5-15%, 20 min
9. 9
   workup.DISSOLUTIONThe mixture was dissolved with DMSO (1 ml)
10. 10
    其他purified by reverse phase HPLC
11. 11
    其他5μ 30×100 mm column, neutral acetonitrile/0.1% formic acid in water, 50-80%, 7 min gradient
12. 12
    洗涤The desired product eluted at 6.8 minutes
13. 13
    浓缩The desired fractions were concentrated to a residue

实验过程

To a 20 ml vial was added methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylate (50.0 mg, 0.169 mmol), (selectfluor) 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate (78 mg, 0.219 mmol) followed with a magnetic stir bar and nitroethane (2 ml). The vial was capped and the reaction stirred at room temperature. Reaction progress was monitored by LCMS. After reaction completion the reaction solvent was removed in-vacuo. The residue was dissolved with DCM (1.4 ml). The DCM solution was charged onto an analogix Si35 SF10-8 gram column. The compound was eluted with EtOAc/Hexanes, 5-15%, 20 min. The desired product and side MW629 co-eluted. The mixture was dissolved with DMSO (1 ml) and purified by reverse phase HPLC using a Gemini 5μ 30×100 mm column, neutral acetonitrile/0.1% formic acid in water, 50-80%, 7 min gradient. The desired product eluted at 6.8 minutes and the side product MW 629 at 9.5 minutes. The desired fractions were concentrated to a residue. LCMS and NMR support the desired structure and analytical HPLC showed 100% purity. The product, methyl 6-bromo-3-fluoro-1-isopropyl-1H-indole-4-carboxylate (11 mg, 0.035 mmol, 20.53% yield), was obtained as a white solid. 1H NMR (400 MHz, METHANOL-d4) δ 7.95 (t, J=1.77 Hz, 1H), 7.78 (d, J=1.77 Hz, 1H), 7.47 (d, J=2.53 Hz, 1H), 4.76-4.84 (m, J=1.64, 6.65, 6.65, 13.36 Hz, 1H), 3.96 (s, 3H), 1.50 (d, 6H). MS (ES)[M+H]+315.1.

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