반응 #1929084

반응 방정식

3,4-difluorophenylboronic acid

compound

3-(5-Bromo-2-methylphenyl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

sodium carbonate

hydrochloric acid

→

3-(3′,4′-Difluoro-4-methylbiphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

용매

ethylene glycol dimethyl ether

반응 조건

후처리

1. 1
   온도under reflux overnight
2. 2
   온도After cooling
3. 3
   추출extracted with ethyl acetate
4. 4
   기타the extract was dried
5. 5
   농축concentrated
6. 6
   기타Purification
7. 7
   기타was carried out by MPLC separation on silica gel using the mobile phase hexane/ethyl acetate 1/1
8. 8
   기타395 mg were then purified again by HPLC [column: Chromatorex C18, 10 μm, 125 mm×30 mm; mobile phase: water/acetonitrile gradient with addition of 0.1% formic acid]

실험 절차

0.74 g (2.0 mmol) of the compound from Example 11A was initially charged in 5 ml of ethylene glycol dimethyl ether, 14.5 ml of 2M aqueous sodium carbonate solution were added dropwise and 10 mg of bis(trisphenylphosphine)palladium(II) chloride were added. 0.35 g (2.2 mmol) of 3,4-difluorophenylboronic acid was then added, and the mixture was stirred under reflux overnight. After cooling, the mixture was acidified with 1N aqueous hydrochloric acid and extracted with ethyl acetate, and the extract was dried and concentrated. Purification was carried out by MPLC separation on silica gel using the mobile phase hexane/ethyl acetate 1/1. This gave 0.7 g (70% of theory) of the title compound. 395 mg were then purified again by HPLC [column: Chromatorex C18, 10 μm, 125 mm×30 mm; mobile phase: water/acetonitrile gradient with addition of 0.1% formic acid]. This gave 121 mg of the title compound.

출처