Hydrochloric Acid → Methyl 2-(2-methyl-4-(trifluoromethyl)phenyl)isonicotinate hydrochloride

HRID 1963215Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][N:17]=1)[C:11]([O:13][CH3:14])=[O:12].[CH3:18][C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=1B(O)O.Cl>C(Cl)Cl.Cl[Pd]Cl.CO>[ClH:7].[CH3:18][C:19]1[CH:24]=[C:23]([C:25]([F:26])([F:27])[F:28])[CH:22]=[CH:21][C:20]=1[C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][N:17]=1)[C:11]([O:13][CH3:14])=[O:12]

Participants

Conditions

Temperature: 100 °C

Procedure

Potassium carbonate (2.66 g, 19.23 mmol), methyl 2-chloroisonicotinate (5.5 g, 32.05 mmol), 2-methyl-4-(trifluoromethyl)phenylboronic acid (8.50 g, 41.67 mmol), PdCl2 (dppf) (0.696 g, 0.96 mmol), and MeOH (50.3 mL) were split into three microwave vials and heated in a single node microwave reactor to 100° C. for 20 min. Diluted with DCM, filtered and evaporated. Purified by flash chromatography using 5% EtOAc in heptane ->20% EtOAc over 10 CV at 280 nm. The residue was dissolved in ether and hydrogen chloride (4 M in dioxane, 8.01 mL, 32.05 mmol) was added and the solvents evaporated to yield methyl 2-(2-methyl-4-(trifluoromethyl)phenyl)isonicotinate hydrochloride (9.15 g, 86%) as a white solid. 1H NMR (400 MHz, cd3od) δ 2.41 (s, 3H), 4.03 (s, 3H), 7.63-7.76 (m, 3H), 8.27 (dd, 1H), 8.33 (dd, 1H), 8.99 (dd, 1H). MS m/z 296 (M+H)+

Workup

filtrationfiltered
customevaporated
customPurified by flash chromatography
dissolutionThe residue was dissolved in ether
customthe solvents evaporated

Sources & evidence

ORD record: ord-0b9e8c77b209496ea8b02ba80fae270b
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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