Sodium Carbonate → 4-[4-Methoxy-3-(phenyl)phenyl]pyridine

HRID 1595255Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)C#N.[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:14][C:13]=1B(O)O.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:14][C:13]=1[C:2]1[CH:3]=[CH:4][CH:7]=[CH:8][CH:9]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A stirred mixture of 3-bromobenzonitrile (0.91 g, 5.0 mmol), 2-Methoxy-5-(pyridin-4-yl)phenylboronic acid (0.50 g, 2.3 mmol), tri-o-tolylphosphine (0.152 g, 0.50 mmol), palladium (II) acetate (0.056 g 0.25 mmol), sodium carbonate (1.59 g, 15 mmol) and water (15 mL) in dimethylformamide (46 mL) is heated at 80° C. for 5 h. The mixture is then treated with water (100 mL) and extracted with ethyl acetate (3×80 mL). The combined extracts are dried (Na2SO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by chromatography (silica gel, ethyl acetate) to give 4-[4-methoxy-3-(phenyl)phenyl]pyridine base. The base is dissolved in diethylether (5 mL), treated with methanolic HCl (excess), evaporated to dryness under reduced pressure and recrystallised from ethanol-ether to give 4-[2-methoxy-3′-cyano-biphenyl-5-yl]pyridine, hydrochloride as a pale-yellow crystalline solid, m.p. 142-150° C.

Workup

extractionextracted with ethyl acetate (3×80 mL)
dry with materialThe combined extracts are dried (Na2SO4)
filtrationfiltered
customthe solvent is evaporated off under reduced pressure
customto yield the crude product which
customis purified by chromatography (silica gel, ethyl acetate)

Sources & evidence

ORD record: ord-1271b06bb0894d8488ee6781e825921f
Source dataset: uspto-grants-2001_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06288092B1

Reaction notes

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