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To a mixture of 5.6 g (3 equiv.) of magnesium and 20 ml of dry diethyl ether there were added first a small amount of iodine and then, over a period of 10 minutes, 5 g of 2-bromothiophene, and stirring was carried out for a further 10 minutes. When the reaction had started, 33.5 g (2.6 equiv.) of 2-bromothiophene dissolved in 80 ml of diethyl ether were added dropwise, and stirring was carried out over a period of 2 hours at room temperature. The Grignard reagent prepared above was added dropwise to a solution of 20 g (1 equiv.) of tert-butyloxycarbonyl-4-cyano-4-(dimethylamino)piperidine dissolved in 200 ml of THF, and stirring was carried out overnight at room temperature. The progress of the reaction was monitored by thin-layer chromatography (50% EtOAc/hexane). When the reaction was complete, the reaction solution was cooled to 0° C., saturated NH4Cl solution was added, extraction with ethyl acetate (3×100 ml) was carried out, and the combined organic phases were dried with Na2SO4. After removal of the solvent under reduced pressure, purification was carried out by column chromatography (Alox Neutral; 30% EtOAc/hexane). 6.1 g (25%) of product were obtained in the form of a white solid.

1. waitwas carried out for a further 10 minutes
2. additionwere added dropwise
3. waitwas carried out over a period of 2 hours at room temperature
4. stirringstirring
5. waitwas carried out overnight at room temperature
6. extractionextraction with ethyl acetate (3×100 ml)
7. dry with materialthe combined organic phases were dried with Na2SO4
8. customAfter removal of the solvent
9. customunder reduced pressure, purification