反应详情

温度

70 °C

A solution of 2-bromothiophene (3.2 ml, 33 mmol) in THF (30 ml) is added dropwise to a mixture of magnesium (0.8 g, 33 mmol) and a single crystal of iodine in THF (30 ml). After addition of just under one half of the 2-bromothiophene the addition is suspended until reaction has initiated (judged by an exotherm). The addition is then completed maintaining the reaction temperature to below 40° C. After the addition is completed the reaction mixture is heated to 70° C. for 1 hour. This mixture is then cooled and added to a solution of oxo-thiophen-2-yl-acetic acid 1-methyl-piperidin-4-yl ester (6.48 g, 25.6 mmol) in THF (80 ml). After the addition is completed the reaction mixture is stirred at room temperature for 1 hour and then heated to reflux for 2 hours. After cooling to room temperature saturated aqueous ammonium chloride solution (100 ml) is added. The solution is extracted with diethylether dried over magnesium sulphate, filtered and concentrated. Purification by flash silica column chromatography gives the title product.

1. additionthe addition
2. customis suspended until reaction
3. additionThe addition
4. temperatureis then completed maintaining the reaction temperature to below 40° C
5. additionAfter the addition
6. temperatureThis mixture is then cooled
7. additionAfter the addition
8. temperatureheated
9. temperatureto reflux for 2 hours
10. additionis added
11. extractionThe solution is extracted with diethylether
12. dry with materialdried over magnesium sulphate
13. filtrationfiltered
14. concentrationconcentrated
15. customPurification by flash silica column chromatography