Reaktion #425507

Reaktionsgleichung

methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate

1-(4-bromo-2-fluorophenyl)cyclobutanol

potassium carbonate

toluene

→

title compound

Ausbeute 57.0%

methyl 6-chloro-5-[3-fluoro-4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylate

Ausbeute 57.0%

Lösungsmittel

ethanol

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas sparged with nitrogen for 10 minutes
2. 2
   SonstigeThe reaction mixture was placed in a pre-heated oil bath at 105° C.
3. 3
   Waschenwashed with water and saturated brine (1× each),
4. 4
   Trocknendried over magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated in vacuo
7. 7
   Sonstigeto afford a brown semi-solid, which
8. 8
   Sonstigewas purified by flash chromatography (12 g silica, 10-50% ethyl acetate/heptane, 21 column volumes)
9. 9
   Einengenconcentrated in vacuo

Vorschrift

A mixture of methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (75 mg, 0.23 mmol), 1-(4-bromo-2-fluorophenyl)cyclobutanol (57 mg, 0.23 mmol), 4M aqueous potassium carbonate (0.47 mL, 0.9 mmol), toluene (3 mL), and ethanol (1 mL) was sparged with nitrogen for 10 minutes, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (9 mg, 0.011 mmol). The reaction mixture was placed in a pre-heated oil bath at 105° C. and stirred for 2 hours. The reaction was cooled to room temperature, diluted with ethyl acetate, washed with water and saturated brine (1× each), dried over magnesium sulfate, filtered and concentrated in vacuo to afford a brown semi-solid, which was purified by flash chromatography (12 g silica, 10-50% ethyl acetate/heptane, 21 column volumes). The product fractions were combined and concentrated in vacuo to afford the title compound as a colorless solid (49 mg, 56% yield). MS (ES−) 372.2 (M−H)−. 1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 8.10 (s, 1H), 7.94 (d, J=2.93 Hz, 1H), 7.54 (s, 1H), 7.38-7.44 (m, 1H), 7.18-7.28 (m, 2H), 3.89 (s, 3H), 2.66-2.77 (m, 2H), 2.42 (m, 2H), 2.11-2.22 (m, 1H), 1.74-1.86 (m, 1H).

Quelle