Reaktion #657292

Reaktionsgleichung

3-(4-bromo-2-chloro-6-methyl-phenyl)-4-hydroxy-8-methoxy-1-methyl-1,8-diaza-spiro[4.5]dec-3-en-2-one

4-chlorophenylboronic acid

sodium carbonate

hydrochloric acid

→

3-(3,4′-Dichloro-5-methyl-biphenyl-4-yl)-4-hydroxy-8-methoxy-1-methyl-1,8-diaza-spiro[4.5]dec-3-en-2-one

Lösungsmittel

dimethoxyethane

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe mixture was heated at 80° C. for 10 hours
2. 2
   Extraktionextracted with ethyl acetate (4×15 ml)
3. 3
   WaschenThe combined organic layers were washed with brine
4. 4
   Trocknendried over sodium sulfate
5. 5
   Einengenconcentrated
6. 6
   SonstigeThe residue was triturated with diethyl ether
7. 7
   workup.STIRRINGstirred at room temperature
8. 8
   Filtrationfiltered
9. 9
   Sonstigedried

Vorschrift

To a solution of 3-(4-bromo-2-chloro-6-methyl-phenyl)-4-hydroxy-8-methoxy-1-methyl-1,8-diaza-spiro[4.5]dec-3-en-2-one (compound P2.34) (150 mg, 0.361 mmol) in dimethoxyethane (10 ml) under argon atmosphere was added tetrakis(triphenyl-phosphine)palladium(0) (25 mg, 0.022 mmol) and the mixture stirred at room temperature for 15 minutes. After further addition of water (2 ml), 4-chlorophenylboronic acid (68 mg, 0.435 mmol) and sodium carbonate (153 mg, 1.444 mmol), the mixture was heated at 80° C. for 10 hours. The reaction mixture was acidified at room temperature to pH 4 with 1N hydrochloric acid and extracted with ethyl acetate (4×15 ml). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was triturated with diethyl ether, stirred at room temperature, filtered and dried. Yield: 114 mg of 3-(3,4′-dichloro-5-methyl-biphenyl-4-yl)-4-hydroxy-8-methoxy-1-methyl-1,8-diaza-spiro[4.5]dec-3-en-2-one as a pale brown solid, mp 236° C. (dec).

Quelle