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

HRID 968027Notes

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 (405 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 C16H18ClNO: 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-d69dee69bb0a406faddb0b7a4817909f
Source dataset: uspto-grants-2005_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06956047B1

Reaction notes

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