Reaktion #90708

Reaktionsgleichung

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

Ausbeute 20.7%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigefollowed with a magnetic stir bar
2. 2
   SonstigeThe vial was capped
3. 3
   SonstigeReaction progress
4. 4
   SonstigeAfter reaction completion the reaction solvent
5. 5
   Sonstigewas 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
   WaschenThe compound was eluted with EtOAc/Hexanes, 5-15%, 20 min
9. 9
   workup.DISSOLUTIONThe mixture was dissolved with DMSO (1 ml)
10. 10
    Sonstigepurified by reverse phase HPLC
11. 11
    Sonstige5μ 30×100 mm column, neutral acetonitrile/0.1% formic acid in water, 50-80%, 7 min gradient
12. 12
    WaschenThe desired product eluted at 6.8 minutes
13. 13
    EinengenThe desired fractions were concentrated to a residue

Vorschrift

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.

Quelle