Dimethylacetamide → 3-(4-(Benzyloxy)phenyl)-5-chloroisonicotinonitrile

HRID 81027Notes

Reaction equation

HRID 81027 reaction equation
Cl[C:2]1[CH:9]=[N:8][CH:7]=[C:6]([Cl:10])[C:3]=1[C:4]#[N:5].[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)C(=O)C>C(OCC)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[CH:9]=[N:8][CH:7]=[C:6]([Cl:10])[C:3]=2[C:4]#[N:5])=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 31374DimethylacetamideHCID 62657Potassium Phosphate, TribasicHCID 27343144-Benzyloxy-phenylboronic acidHCID 111375993,5-Dichloropyridine-4-carbonitrile

Product 1

HCID 669269953-(4-(Benzyloxy)phenyl)-5-chloroisonicotinonitrileYield 52%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

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).

Workup

  1. washwashed twice with 1:1 mixture of brine and water (100 mL), brine (100 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. washeluting with 10-35% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-7f0697c79abd40e9b5ca3eb12c8233d1
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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