18-Crown-6 → Ethyl 3-chloro-5-(2-methylphenyl)-1,2-thiazole-4-carboxylate

HRID 2177278Notes

Reaction equation

[Cl:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:5](Cl)[S:4][N:3]=1.[CH3:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O.[F-].[K+].C1OCCOCCOCCOCCOCCOC1>CC(=O)OCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:5]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[CH3:13])[S:4][N:3]=1

Participants

Conditions

Temperature: 110 °C

Procedure

Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed ethyl 3,5-dichloro-1,2-thiazole-4-carboxylate (1 g, 4.42 mmol, 1.00 equiv), (2-methylphenyl)boronic acid (665 mg, 4.89 mmol, 1.11 equiv), Pd(OAc)2 (49.7 mg, 0.22 mmol, 0.05 equiv), KF (773 mg), 18-Crown-6 (117 mg, 0.44 mmol, 0.10 equiv), Tol (40 mL). The resulting solution was stirred overnight at 110° C. in an oil bath. The resulting solution was diluted with 50 mL of EA. The resulting mixture was washed with 5×30 mL of sodium chloride(aq). The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (0:100). This resulted in 730 mg (59%) of ethyl 3-chloro-5-(2-methylphenyl)-1,2-thiazole-4-carboxylate as yellow oil.

Workup

customInto a 100-mL round-bottom flask purged
temperaturemaintained with an inert atmosphere of nitrogen
washThe resulting mixture was washed with 5×30 mL of sodium chloride(aq)
dry with materialThe mixture was dried over anhydrous sodium sulfate
concentrationconcentrated under vacuum
customThis resulted in 730 mg (59%) of ethyl 3-chloro-5-(2-methylphenyl)-1,2-thiazole-4-carboxylate as yellow oil

Sources & evidence

ORD record: ord-26e8cee276a44041ae62f50243798452
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067898B1

Reaction notes

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