Ethyloxalyl chloride

Oxo-4//-thieno[2,3-(/][l,3]oxazines (332), which are available from 2-aminothiophene-3-carboxylic acids by introduction of a one-carbon unit either from acetic anhydride or from ethyloxalyl chloride, react with amines to give thieno[2,3-d]pyrimidin-4(3/i)-ones (Scheme 94) (72JMC106,79JMC505). 

Stannous chloride dihydrate 4-Chloro-3,5-dinitrobenzonitrile Ethyloxalyl chloride Concentrated hydrochloric acid... 

The Step 4 product (3.88 mmol) was dissolved in 100 ml THF, then treated with 3.10ml 1.5M butyllithium in hexanes, then cooled to -78°C, and further treated with 867 (xl cooled ethyloxalyl chloride dissolved in 10 ml THF. The mixture was stirred 5 minutes and then returned to ambient temperature where it was quenched with saturated NH4C1 solution. It was extracted with EtOAc, washed with saturated brine solution, dried, and concentrated. The residue was purified by chromatography using hexane/EtOAc, 1 2, and 212 mg product isolated as a colorless oil. 

The synthesis starts at ethyloxalyl chloride. Reaction with the appropriate aniline and triethylamine as auxiliary base results in a general synthon from which a second wingtip group can be introduced via reaction with a (functionalised) amine (see Figure 4.15). In the present case, the second amine is a o-hydroxyaniUne that introduces the phenoxy... 

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