Dimethylacetamide → 3-Chloro-5-(3-methoxyphenyl)isonicotinonitrile

HRID 81043Notes

Reaction equation

Cl[C:2]1[CH:9]=[N:8][CH:7]=[C:6]([Cl:10])[C:3]=1[C:4]#[N:5].[CH3:11][O:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=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]>[Cl:10][C:6]1[CH:7]=[N:8][CH:9]=[C:2]([C:17]2[CH:16]=[CH:15][CH:14]=[C:13]([O:12][CH3:11])[CH:18]=2)[C:3]=1[C:4]#[N:5]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 3,5-dichloroisonicotinonitrile (2 g, 11.56 mmol), 3-methoxyphenylboronic acid (1.932 g, 12.72 mmol), potassium phosphate (4.91 g, 23.12 mmol) and palladium tetrakis(triphenylphosphine) (0.668 g, 0.578 mmol) was pumped and backfilled with nitrogen 3 times. N,N-dimethylacetamide (30 mL) was added. The mixture was again pumped and backfilled with nitrogen 3 times. After heating to 110° C. for 15 h, the mixture was diluted with ethyl acetate (300 mL), washed with water (50 mL), brine (50 mL) and dried (MgSO4) and concentrated. Silica gel chromatography, loading with dichloromethane-hexanes (1:1) and eluting with 5-30% ethyl acetate in hexanes, gave 3-chloro-5-(3-methoxyphenyl)isonicotinonitrile as white solid (1.20 g, 43% yield). MS (ES+) m/z: 245 (M+H); LC retention time: 3.13 min (analytical HPLC Method A).

Workup

washwashed with water (50 mL), brine (50 mL)
dry with materialdried (MgSO4)
concentrationconcentrated
washeluting with 5-30% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-973377fd55fd4478bb800c9feb9cc30c
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846673B2

Reaction notes

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