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Stage #1: N'-(1-ethylpiperidin-4-ylidene)-4-methylbenzenesulfonohydrazide With N,N,N,N,-tetramethylethylenediamine; isopropylmagnesium chloride for 3h; Reflux;
Stage #2: 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane for 3h; Reflux;
2
The sulfonyl hydrazide compound (49 g, 0.18 mol), isopropylmagnesium chloride solution (370 mL, 1.0 M), tetramethylethylenediamine (23 g, 0.2 mol) were mixed and reacted at 40 ° C for 3 h. Methylboronic acid pinacol ester (26.5 g, 0.19 mol) was added, and the reaction was carried out for 2 h, and then the temperature was raised to reflux for 1 h. After completion of the reaction, the solvent was distilled off, and the product cyclohexene-1-boronic acid pinacol ester was further distilled off at about 100 ° C to obtain 27.5 g of a yield of 89%
Stage #1: C7H12BrN With isopropylmagnesium bromide In tetrahydrofuran
Stage #2: 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran at 0℃; for 6h; Inert atmosphere; Reflux;
3.3
In the third step, 19.1 g (0.1 mol) of N-Et piperidin-4-enyl bromide and 12.9 g (0.105 mol) of isopropyl bromide are subjected to a Grignard exchange reaction in tetrahydrofuran. Then, under the protection of nitrogen, At 0 ° C, 19.03 g (0.11 mol) of pinacol methoxyboronic acid was added dropwise to the reaction solution, the reaction was held for 4 h, and then heated to reflux for 2 h. After the reaction was completed, 20 ml of 10% dilute hydrochloric acid was added to quench the reaction. After the solvent was distilled off, the temperature was further raised to 120 ° C. under reduced pressure to obtain 18.73 g of a target product as a pale yellow liquid with a yield of 79%.
With potassium borohydride In acetonitrile at -10 - 20℃;
5 Example 5
In a 500mL three-necked bottle, add pyridine-4-boronic acid pinacol ester (20.5g, 0.1mol), bromoethane (27.2g, 0.25mol) and acetonitrile (110mL),After stirring evenly, put it in a autoclave and seal it. The temperature was raised to 80 ° C to react overnight, and the raw material reaction was detected to be completed. After evaporating the solvent under reduced pressure, 31.5 g of off-white solid quaternary salt was obtained.The solid was added to 180 mL of acetonitrile to form a suspension, cooled to -10 ° C, and potassium borohydride (6.5 g, 0.12 mol) was added in portions,There are obvious bubbles generated during the addition process, accompanied by exothermic heat, and the temperature should not exceed 0 ° C during each addition.After the addition is complete, return to room temperature naturally and continue stirring overnight. TLC detects the completion of the reaction.The saturated ammonium chloride solution was carefully quenched and extracted with ethyl acetate,Combine the organic layers and evaporate to dryness. Dissolve and filter with ethyl acetate. Rotate to dryness again. After beating with cyclohexane,20.4 g of light yellow solid was obtained, with a yield of 86%, GC: 98.5%, HNMR was consistent with the standard nuclear magnetic spectrum in the literature, and the structure was confirmed to be correct.
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