Tris(1,1-dimethylethyl)phosphine → 3'-Amino-4,2',6'-trifluorobiphenyl-2-carbonitrile
Reaction equation
Br[C:2]1[C:3]([F:10])=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=1[F:8].[F:11][C:12]1[CH:13]=[CH:14][C:15](B2OC(C)(C)C(C)(C)O2)=[C:16]([CH:19]=1)[C:17]#[N:18].[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCCC1.O.O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:9][C:4]1[C:3]([F:10])=[C:2]([C:15]2[C:16]([C:17]#[N:18])=[CH:19][C:12]([F:11])=[CH:13][CH:14]=2)[C:7]([F:8])=[CH:6][CH:5]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 50 °C
Procedure
A solution of 3-bromo-2,4-difluorophenylamine (5.2 g, 25 mmol) and 5-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile (7.10 g, 28.8 mmol) in tetrahydrofuran (95 ml) and water (5 ml) was treated with potassium fluoride (4.8 g, 82.5 mmol) and this mixture was degassed with nitrogen for 10 min before adding tris(dibenzylideneacetone)dipalladium(0) (460 mg, 0.5 mmol) and tri-tert-butylphosphine (2.5 ml of a 0.2M solution in 1,4-dioxane, 0.5 mmol). The reaction was then heated at 50° C. for 2 h then cooled to ambient temperature. The mixture was poured into ice-cold 0.5N sodium hydroxide (750 ml), stirred for 10 min and the solid collected by filtration. This was triturated with water and dried to afford 3′-amino-4,2′,6′-trifluorobiphenyl-2-carbonitrile as a grey powder (6.6 g). Used without further purification: δH (360 MHz, CDCl3) 3.74 (2H, br), 6.79-6.89 (2H, m), 7.36-7.42 (1H, m), 7.45-7.51 (2H, m).
Workup
- customthis mixture was degassed with nitrogen for 10 min
- temperaturethen cooled to ambient temperature
- filtrationthe solid collected by filtration
- customThis was triturated with water
- customdried
Sources & evidence
- ORD record
- ord-514f226fdce646a5847069c64f96fd75
- Source dataset
- uspto-grants-2005_05
- Patent number
- US06900215B2
Reaction notes
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