Synthetic Route of 16793-91-2, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 16793-91-2 name is 2-Chlorophenethyl Bromide, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.
General procedure: Ethyl 2-piperidin-4-ylacetate 11 (1 g, 5.84 mmol, 1.0 equiv.) and substituted (2-romoethyl)benzene derivatives (12a-b) (7.01 mmol, 1.2 equiv.) were dissolved in 20 mL acetone.Then, anhydrous K2CO3 (11.68 mmol, 2 equiv.) and catalytic amount KI were added. The reactionmixture was refluxed for 4 h. After completion of the reaction, acetone was concentrated, and theresidue was dissolved in water (60 mL) and extracted with ethyl acetate (60 ¡Á 3 mL). The combinedorganic layers were dried over Na2SO4, filtered, and concentrated in vacuum. The obtained oil wasused in further synthesis without purification yielded compounds 13a-b (Yields were 67% and 72%).Then, 4 mol/L KOH (2.5 equiv.) was added to the solution of compounds 13a-b in C2H5OH: H2O =5:1(6 mL). The reaction mixture was stirred at room temperature for 7 h. After completion of the reaction, the reaction mixture was evaporated to dryness after neutralization with dilute hydrochloricacid solution. Poured into ethyl acetate to deposit the solid, after cooling off, the mixture was filteredand washed with cold ethyl acetate to give compounds 14a-d.Finally, intermediates (14a-b) (1.2 equiv.), PyBOP (1.2 equiv.) and DIPEA (1.5 equiv.) wereadded to 6 mL DMF and stirred at room temperature for 20 min. Then, intermediates (15a-b) (1.0equiv.) was added and stirred at room temperature for 4 h. After completion of the reaction, thereaction mixture was quenched with saturated NaCl solution. The aqueous phase was extracted withDCM. The DCM layer was combined and washed with brine solution. The organic layer was driedover anhydrous Na2SO4 and the solvent was removed under reduced pressure. After concentration,the crude product was purified by silica gel column chromatograph using a methanol indichloromethane gradient (DCM:methanol = 60:1-5:1) yielded compounds 16a-d.N-(1H-Indol-5-yl)-2-(1-phenethylpiperidin-4-yl)acetamide (16a). 2-(1-Phenethylpiperidin-4-yl) aceticacid (140 mg, 0.57 mmol), 1H-Indol-5-amine (63 mg, 0.48 mmol), PyBOP (295 mg, 0.57 mmol),DIPEA (93 mg, 0.72 mmol), DMF (6 mL). Yellow solid, m.p.: 165-167 C, yield: 80.70%, 1H NMR(400 MHz, CD3OD) delta 7.74 (d, J = 2.0 Hz, 1H), 7.28 (tt, J = 13.1, 6.8 Hz, 6H), 7.20 (d, J = 3.1 Hz, 1H),7.15 (dd, J = 8.6, 2.0 Hz, 1H), 6.37 (d, J = 3.1 Hz, 1H), 3.60 (d, J = 14.9 Hz, 2H), 3.26 (d, J = 5.0 Hz, 1H),3.08-3.01 (m, 3H), 2.39 (d, J = 7.0 Hz, 2H), 2.21-2.13 (m, 1H), 2.04 (d, J = 15.4 Hz, 2H), 1.74-1.60 (m,2H), 1.27 (s, 2H). 13C NMR (151 MHz, CD3OD) delta 170.66, 136.38, 133.81, 129.79, 128.59, 128.42, 127.97,126.86, 125.29, 115.83, 115.76, 112.47, 110.75, 101.07, 72.24, 70.09, 60.80, 57.69, 53.42, 52.37, 41.90,31.68, 31.23, 29.38, 28.89, 22.34, 13.05. HRMS (ESI): calcd. For C23H27N3O [M + H]+ 362.2227, found362.2242.
At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chlorophenethyl Bromide, and friends who are interested can also refer to it.
Reference:
Article; Guo, Yan; Yang, Hongyu; Huang, Zhongwei; Tian, Sen; Li, Qihang; Du, Chenxi; Chen, Tingkai; Liu, Yang; Sun, Haopeng; Liu, Zongliang; Molecules; vol. 25; 3; (2020);,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics