반응 #1151444

반응 방정식

tri-tert-butylphosphine

sodium hydroxide

1-(3-Chloro-4-fluorophenyl)ethanone

2-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzonitrile

potassium fluoride

→

5′-acetyl-2′-fluorobiphenyl-2-carbonitrile

수율 26.0%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   기타the mixture degassed with nitrogen for 30 min
2. 2
   온도then heated at 50° C. for 18 h
3. 3
   온도to cool to room temperature
4. 4
   workup.STIRRINGstirred for 30 min
5. 5
   여과The solid was filtered
6. 6
   세척washed with water (50 ml) and isohexane (50 ml)
7. 7
   workup.WAITthe brown solid left
8. 8
   기타to air-dry
9. 9
   기타The solid was purified by flash column chromatography on silica eluting with isohexane on a gradient of ethyl acetate (10-30%)
10. 10
    기타Collecting the appropriate fractions

실험 절차

1-(3-Chloro-4-fluorophenyl)ethanone (0.86 g, 5.0 mmol), 2-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzonitrile (1.37 g, 6.0 mmol) (prepared according to the procedure described in WO 02/74773) and potassium fluoride (0.96 g, 16.5 mmol) were suspended in tetrahydrofuran (20 ml) and the mixture degassed with nitrogen for 30 min. Tris(dibenzylidineacetone)dipalladium(0) (0.14 g, 0.15 mmol) and tri-tert-butylphosphine (0.3M in 1,4-dioxane, 1.0 ml) were added and the mixture stirred at room temperature for 1 h then heated at 50° C. for 18 h. The mixture was allowed to cool to room temperature and then poured into 0.5N sodium hydroxide solution (300 ml) and stirred for 30 min. The solid was filtered, washed with water (50 ml) and isohexane (50 ml) and the brown solid left to air-dry. The solid was purified by flash column chromatography on silica eluting with isohexane on a gradient of ethyl acetate (10-30%). Collecting the appropriate fractions gave 5′-acetyl-2′-fluorobiphenyl-2-carbonitrile (0.31 g, 26%) as a yellow solid: δH(400 MHz, CDCl3) 2.64 (3H, s), 7.31 (1H, t, J 8.8 Hz), 7.52-7.56 (2H, m), 7.68-7.72 (1H, m), 7.81 (1H, dd, J 0.8, 7.4 Hz), 8.04-8.09 (2H, m).

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