Methanol → Methyl 2-(3,5-dichlorophenyl)isonicotinate

HRID 1963188Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].Cl[C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][N:17]=1)[C:11]([O:13][CH3:14])=[O:12].[Cl:18][C:19]1[CH:20]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:22]=[C:23]([Cl:25])[CH:24]=1.CO>O.C(Cl)Cl.Cl[Pd]Cl>[Cl:18][C:19]1[CH:20]=[C:21]([C:8]2[CH:9]=[C:10]([CH:15]=[CH:16][N:17]=2)[C:11]([O:13][CH3:14])=[O:12])[CH:22]=[C:23]([Cl:25])[CH:24]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Potassium carbonate (2.416 g, 17.48 mmol), methyl 2-chloroisonicotinate (5 g, 29.14 mmol), 2-(3,5-dichlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (10.34 g, 37.88 mmol), PdCl2 (dppf) (0.633 g, 0.87 mmol), and MeOH (45.7 mL) were split in three 20 mL microwave-vials and heated to 100° C. in a single node microwave reactor for 20 min. The reaction mixture was diluted with water and DCM, the aqueous layer extracted with DCM and the combined organic layers were evaporated. Purified by automated flash chromatography using 5% EtOAc in heptane ->30% EtOAc over 15 CV at 280 nm. Methyl 2-(3,5-dichlorophenyl)isonicotinate (6.1 g, 74%) was isolated as a white powder. 1H NMR (400 MHz, cdcl3) δ 4.01 (s, 3H), 7.44 (t, 1H), 7.84 (dd, 1H), 7.96 (d, 2H), 8.23-8.28 (m, 1H), 8.85 (dd, 1H).

Workup

extractionthe aqueous layer extracted with DCM
customthe combined organic layers were evaporated
customPurified by automated flash chromatography

Sources & evidence

ORD record: ord-7e345f6b97644950a445193dc3d4d890
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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