Reaktion #168209

Reaktionsgleichung

N,N-Dimethylacetamide

3,5-dichloroisonicotinonitrile

4-(benzyloxy)phenylboronic acid

potassium phosphate

→

3-(4-(benzyloxy)phenyl)-5-chloroisonicotinonitrile

Ausbeute 52.0%

Lösungsmittel

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenwashed twice with 1:1 mixture of brine and water (100 mL), brine (100 mL)
2. 2
   Trocknendried (MgSO4)
3. 3
   Einengenconcentrated
4. 4
   Wascheneluting with 10-35% ethyl acetate in hexanes

Vorschrift

A mixture of 3,5-dichloroisonicotinonitrile (2.50 g, 14.45 mmol), 4-(benzyloxy)phenylboronic acid (3.63 g, 15.90 mmol), potassium phosphate (6.13 g, 28.9 mmol) and palladium tetrakis(triphenylphosphine) (0.835 g, 0.723 mmol) was pumped and backfilled with nitrogen 3 times. N,N-Dimethylacetamide (40 mL) was added. The mixture was again pumped and backfilled with nitrogen 3 times and heated with a 150° C. oil bath for 1 h. The mixture was diluted with ethyl acetate (400 mL), washed twice with 1:1 mixture of brine and water (100 mL), brine (100 mL), dried (MgSO4) and concentrated. Silica gel chromatography, loading with toluene and eluting with 10-35% ethyl acetate in hexanes, gave 3-(4-(benzyloxy)phenyl)-5-chloroisonicotinonitrile as a white solid (2.387 g, 52% yield). 1H NMR (500 MHz, CDCl3) δ ppm 8.72 (1H, s), 8.69 (1H, s), 7.51-7.60 (2H, m), 7.40-7.50 (4H, m), 7.33-7.40 (1H, m), 7.10-7.19 (2H, m), 5.15 (2H, s); MS (ES+) m/z: 321 (M+H); LC retention time: 4.323 min (analytical HPLC Method A).

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