反应详情

温度

-78 °C

Under inert conditions, add a 2.0 M solution (in tetrahydrofuran/n-heptane) of lithium diisopropylamide (29.65 mmol, 14.83 mL, 1.05 equivalents) to a cold (−78° C.) solution of 3-bromo-4-methylthiophene (28.24 mmol, 5.00 g, 1.00 equivalents) in dry tetrahydrofuran (27.33 mL). Stir at −78° C. for 1 hour and add a solution of 4-(methoxy-methyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (28.24 mmol, 7.69 g, 1.00 equivalents), dropwise. Continue stirring at −78 ° C. for 3 hours. Quench the reaction mixture with saturated ammonium chloride (aqueous, 55 mL) and allow to warm to room temperature. Extract the reaction mixture with a mixture of ethyl acetate : diethyl ether (1:1, 3×40 mL). Combine the extracts and dry over magnesium sulfate, filter and evaporate. Purify the residue via flash column chromatography using a mixture of n-heptane:ethyl acetate (4:1) to yield a yellow, crystalline solid (9.84 g).

1. stirringContinue stirring at −78 ° C. for 3 hours
2. customQuench the reaction mixture with saturated ammonium chloride (aqueous, 55 mL)
3. temperatureto warm to room temperature
4. extractionExtract the reaction mixture
5. additionwith a mixture of ethyl acetate : diethyl ether (1:1, 3×40 mL)
6. dry with materialCombine the extracts and dry over magnesium sulfate
7. filtrationfilter
8. customevaporate
9. customPurify the residue via flash column chromatography
10. additiona mixture of n-heptane:ethyl acetate (4:1)