Hydrochloric Acid → HCID 25024042, compound

Participants

Reaction Steps

Dissolve diethyl-carbamic acid 2-(4-methoxy-phenyl)-1-oxo-3-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-1H-1Lambda*4*-benzo[b]thiophen-6-yl ester (Example 1) (4.0 g, 6.8 mmol) in 80 mL n-propyl alcohol with stirring and then cool the resultant solution to −10° C. Add 37% hydrochloric acid (6.7 g, 67 9 mmol) dropwise at −10° C. within a 10 minute time period. After the mixture is warmed up to ambient temperature, add Na2S2O3.5H2O (6.7 g, 27 0 mmol) and allow the reaction to occur at ambient temperature for 4 hours. Monitor the reaction by 11H NMR for completion. Carefully add 100 mL of saturated aqueous NaHCO3 to neutralize the reaction mixture and then adjust the pH of the mixture to 7. Add 100 mL CH2Cl2 and stir. Separate the organic phase, and extract the aqueous phase with CH2Cl2 (2×50 mL). Wash (with successive washes) the combined organic phase with brine (50 mL) and water (50 mL), dry over anhydrous Na2SO4, and filter. Remove all the volatiles under reduced pressure, affording 3.4 g of the crude product as a viscous material. Pass this viscous material through a short pad of silica gel with 100% petroleum ether (30-60° C.) and 100% ethyl acetate as the eluents. Collect the ethyl acetate phase and evaporate all the volatiles under reduced pressure, producing 3.2 g of the crude product as a pale yellow viscous material. Add 20 mL of hexane and the mixture is kept at 4° C. overnight, affording the desired product Diethyl-carbamic acid 2-(4-methoxy-phenyl)-3-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-benzo[b]thiophen-6-yl ester as a white solid (2.9 g, yield 74%, NMR purity>96%) after dried at 40° C./2 mmHg.

Provenance & Evidence