Chloroform → 4-Chloro-2,5-dimethyl-6-(2,4,6-trimethyl-phenoxy)pyridine

HRID 1831708Notes

Reaction equation

[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[OH:10].[H-].[Na+].Cl[C:14]1[C:19]([CH3:20])=[C:18]([Cl:21])[CH:17]=[C:16]([CH3:22])[N:15]=1.C(Cl)(Cl)Cl>CS(C)=O.CCCCCC>[Cl:21][C:18]1[CH:17]=[C:16]([CH3:22])[N:15]=[C:14]([O:10][C:3]2[C:4]([CH3:9])=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=2[CH3:1])[C:19]=1[CH3:20]

Participants

Conditions

Temperature: 130 °C

Procedure

A solution of 2,4,6-trimethylphenol (450 mg, 3.31 mmol) in 2 ml of DMSO was treated with NaH (60% in oil, 180 mg, 4.5 mmol). After 5 min, 2,4-Dichloro-3,6-dimethyl-pyridine (528 mg, 3 mmol) was added. The mixture was heated in the oil bath of 130° C. for 6 hours. The mixture was quenched with water and extracted with EtOAc. The organic layer was dried and concentrated to give 812.5 mg of crude material with two regioisomers. After silica gel column chromatography using 1:1 of CHCl3:hexane as eluent, the title compound was isolated as white crystals (141 mg), mp 57–62° C.; high MS for C16H18CINO: calc, 275.1072, found 275.70172; IR(KBr) 2951, 2920, 1592, 1564 cm-1; 1H NMR (CDCl3) δ 6.87 (s, 2H), 6.77 (s, 1H), 2.39 (s, 3H), 2.29 (s, 3H), 2.18 (s, 3H), 2.03 (s, 6H) ppm. The regiochemistry was determined by X-ray structural analysis of the undesired regioisomer, 2-chloro-3,6-dimethyl-4-(2,4,6-trimethyl-phenyoxy)-pyridine.

Workup

customThe mixture was quenched with water
extractionextracted with EtOAc
customThe organic layer was dried
concentrationconcentrated
customto give 812.5 mg of crude material with two regioisomers

Sources & evidence

ORD record: ord-6f8e7c7033fa4f6db26285cdc67ebb98
Source dataset: uspto-grants-2006_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07067664B1

Reaction notes

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