4-Toluenesulfonyl chloride → methyl 1,1-dimethyl-3-(pyrid-3-yl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxylate

Participants

Reaction Steps

To a solution of p-toluenesulfonyl chloride (18 g, 95 mmol) and methyl 2,3-dichloropropionate (15 g, 95 mmol) in refluxing CH2Cl2 (125 mL) was added a mixture of 2-(3-pyridinyl)-3-formyl-5,5-dimethyl-4-thiazolidinecarboxylic acid (5.1 g, 19 mmol) and triethylamine (2.3 g, 22 mmol) in CH2Cl2 (125 mL). After one hour at reflux triethylamine (4.6 g, 44 mmol) was added and the reaction mixture was refluxed for a further 17 hours. The reaction mixture was cooled to ambient temperature and partitioned between cold 1N aqueous NaOH and ethyl acetate. The organic phase was washed with cold 1N aqueous NaOH and brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was dissolved in 5% aqueous HCl and the solution was extracted twice with ether. The aqueous phase was neutralized with solid Na2CO3 and extracted twice with ethyl acetate. The combined ethyl acetate extracts where washed with brine, dried over MgSO4, and concentrated in vacuo. Chromatography on silica gel (150 g, 1:1 ethyl acetate, hexanes), afforded methyl 1,1-dimethyl-3-(pyrid-3-yl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxylate (1.1 g, 20%) as an off-while powder.

Provenance & Evidence