Reaction #554612

Reaction equation

Ethyl 6-bromo-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate

phenylboronic acid

potassium phosphate trihydrate

→

Ethyl 6-phenyl-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate

Solvents

dioxane

Conditions

Workup

1. 1
   workup.ADDITIONwere added to the mixture
2. 2
   OtherThe microwave vial was capped
3. 3
   Otherirradiated at 100 watt, 150° C., under pressure up to 10 bars
4. 4
   Othertoluene was removed under reduced pressure
5. 5
   workup.DISSOLUTIONthe residue was dissolved in dichloromethane
6. 6
   Washwashed with water
7. 7
   DryingThe organic layer was dried over magnesium sulfate
8. 8
   Filtrationfiltered
9. 9
   Otherevaporated to dryness
10. 10
    OtherThe residue was purified by silica gel column chromatography
11. 11
    Otherto yield a light-beige-colored solid in 70-80%

Procedure

Ethyl 6-bromo-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate (0.185 g, 0.500 mmol), phenylboronic acid (0.76 g, 0.625 mmol, 1.2 equiv.) and potassium phosphate trihydrate (0.200 g, 0.750 mmol, 1.5 equiv.) were mixed together in a 10 ml microwave vial. The vial was purged with Argon and trans-dichlorobis(triphenylphosphine)-palladium (II) (0.0105 g, 0.015 mmol, 3 mol %) and 5 ml of dry dioxane were added to the mixture. The microwave vial was capped and irradiated at 100 watt, 150° C., under pressure up to 10 bars. Then it was allowed to cool down to rt, and toluene was removed under reduced pressure and the residue was dissolved in dichloromethane and washed with water. The organic layer was dried over magnesium sulfate, filtered, and evaporated to dryness. The residue was purified by silica gel column chromatography using 20% of ethyl acetate/cyclohexane as eluent to yield a light-beige-colored solid in 70-80%. 1H-NMR (DMSO-d6) δ 1.11, 1.35 (each t, 3H, 3J=7.1 Hz, CH3); 2.60 (m, 2H, 2′-H); 3.31 (m, 2H, 1′-H); 3.99, 4.35 (each q, 2H, 4J=7.1 Hz, CH2); 7.35 (m, 2H, 4-H, 5-H); 7.46 (m, 2H, 2″-H, 6″-H); 7.62 (dd, 1H, 4″-H); 7.65 (m, 2H, 3″-H, 5″-H); 7.75 (dd, 1H, 7-H); 11.63 (s, 1H, NH). 13C-NMR (DMSO-d6) δ 14.9, 15.1 (2CH3, each C═OOCH2CH3); 20.90 (C-2′); 35.9 (C-1′); 60.7, 61.2 (2CH2, each C═OOCH2CH3); 111.0 (C-7); 120.1 (C-4); 121.8 (C-3); 122.3 (C-3a), 124.8 (C-5) 127.2 (C-2″, C-6″); 127.7 (C-4″); 128.0 (C-3″, C-5″); 129.8 (C-2); 137.7 (C-7a); 138.2 (C-6); 141.9 (C-1″); 162.3 (2′-CO2Et); 173.1 (2-CO2Et). LC-MS (m/z): 383 [M-NH4+]+, 366 [M]+, 364 [M]−. Purity LC-MS: 96%.

Source