Dimethylformamide → N-[5-chloro-3-(2-methoxyethyl)-1,3-thiazol-2(3H)-ylidene]acetamide

HRID 255114Notes

Reaction equation

[C:1]([NH:4][C:5]1[S:6][C:7]([Cl:10])=[CH:8][N:9]=1)(=[O:3])[CH3:2].CN(C=O)C.[H-].[Na+].[CH3:18][O:19][CH2:20][CH2:21]Br>C(OCC)(=O)C>[Cl:10][C:7]1[S:6][C:5](=[N:4][C:1](=[O:3])[CH3:2])[N:9]([CH2:21][CH2:20][O:19][CH3:18])[CH:8]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A flask was charged with 2-acetamido-5-chlorothiazole (Lancaster, 19.3 g, 110 mmol) in 200 mL of 2:1 THE/DMF. To the solution was added sodium hydride (60% dispersion in mineral oil, 5.44 g, 142 mmol). The mixture was stinred at room temperature for 15 minutes and then 2-bromoethyl methyl ether (18.3 g, 131 mmol) was added. The mixture was warmed to 85° C. and stirred overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate and washed with water. The organic extract was dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography on SiO2 using a gradient of 0% to 100% ethyl acetate:hexane to provide 10.3 g (42%) of the title compound as the more polar regioisomer: 1H NMR (300 MHz, CDCl3) δ 2.28 (s, 3 H) 3.35 (s, 3 H) 3.65-3.71 (m, 2 H) 4.28-4.36 (m, 2 H) 7.00 (s, 1 H); MS (ESI+) m/z 235 (M+H)+.

Workup

temperatureAfter cooling to room temperature
washwashed with water
extractionThe organic extract
dry with materialwas dried (MgSO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography on SiO2 using a gradient of 0% to 100% ethyl acetate

Sources & evidence

ORD record: ord-4663bc948be54dfea1620a5e16e59f97
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07875639B2

Reaction notes

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