Sodium Bicarbonate → 4'-Fluoro-2'-methoxy-3-trifluoromethyl-biphenyl-4-carbonitrile

HRID 585581Notes

Reaction equation

Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1.C([O-])(O)=O.[Na+].[F:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[C:22]([O:29][CH3:30])[CH:21]=1>C1(C)C=CC=CC=1.CCO.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=2)=[C:22]([O:29][CH3:30])[CH:21]=1

Participants

Conditions

Temperature: 95 °C

Procedure

In a round bottom flask under argon, 4-bromo-2-trifluoromethylbenzonitrile (1 g, 4 mmol) was solubilized in a mixture of toluene (55 mL) and EtOH (20 mL). Aq. NaHCO3 (20 ml, 5 eq., 0.8 M solution) and 4-fluoro-2-methoxyphenylboronic acid (816 mg, 4.8 mmol) were added. The mixture was degassed under the stream of argon for 10 min. Then Pd(PPh3)4 (462 mg, 0.4 mmol) was added and the mixture was heated at 95° C. for 2 hr. After it was cooled, the mixture was poured in brine and extracted with CH2Cl2. This organic layer was dried (MgSO4), filtered and evaporated. Chromatography on a silica gel (250 ml, EtOAc:hexanes, 1:9), gave a white solid (951 mg, 81%), 1H NM (300 MHz, acetone-d6)δ: 8.02-8.14 (m, 3H, C2,5,6—H), 7.53 (dd, 1H, J=8, 7 Hz, C6′—H), 7.03 (dd, 1H, J=11, 2 Hz, C3′—H), 6.89 (td, 1H, J=8, 2Hz, C5′—H).

Workup

customThe mixture was degassed under the stream of argon for 10 min
temperatureAfter it was cooled
extractionextracted with CH2Cl2
dry with materialThis organic layer was dried (MgSO4)
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-5e9422330af34dbcacaf82cbaef32e18
Source dataset: uspto-grants-2005_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06933321B2

Reaction notes

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