154127-42-1, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact.154127-42-1,(S)-4-Hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide, it is a common compound, a new synthetic route is introduced below.
Compound B (50.0 g, 140.7 mmol) was added to 450 mL of acetonitrile, trimethyl orthoacetate (27.0 g, 225.1 mmol) and triethylamine (1.4 g, 14.0 mmol) were added with stirring, and the mixture was heated to 78C. , stirring for 5h,HPLC monitoring showed complete reaction and the HPLC monitoring results are shown in Table 1 (see FIG. 1).Cool to 40C, distill off under reduced pressure, and concentrate to a minimum volume.Compound C crude product was obtained.The crude compound C was dissolved in 180 mL of tetrahydrofuran, cooled to -10 DEG C, triethylamine (31.3 g, 309.5 mmol) was slowly added dropwise at a drip rate of 1 d/s, and the addition was completed at a drip rate of 3 d/s. 4- A solution of tosyl chloride (53.5 g, 280.6 mmol) in 70 mL of tetrahydrofuran. After the addition, the temperature was controlled at -4C, and the reaction was complete after about 3 hours.At a controlled temperature of 10 C. or less, a 70% aqueous solution of ethylamine (361.0 g, 5.6 M) was slowly added dropwise at a rate of 5 d/s. After the addition, the temperature was kept stirring at 12C and the reaction was complete after about 15 hours.The mixture was concentrated under reduced pressure to 70-80 mL, and the temperature was lowered to 0C. The temperature was controlled below 30C, and concentrated hydrochloric acid (12 mol/L) was added dropwise to adjust the pH to 1 to 2, and then about 14 mL of concentrated hydrochloric acid (12 mol/L) was added. The mixture was stirred at room temperature for 1 hour. The reaction was extracted twice with methyl tert-butyl ether (2*250 mL). The organic phases were combined and extracted once with dilute hydrochloric acid (1 mol/L, 100 mL). Combine the aqueous phases, slowly add sodium bicarbonate solids, adjust the pH to 5-6, add 150 mL of water, and adjust the pH to 7-8 with 7% sodium bicarbonate solution. After adjustment, stir at room temperature for 15 h and slowly crystallize. After filtration, the filter cake was rinsed with 30 mL of water and the cake was dried to obtain 35.4 g of product with a purity of 98.3%.Add 250 mL of dichloromethane, 25 mL of methanol to the filter mother liquor, stir, extract, separate, and concentrate the organic phase to dryness4.6 g of yellow viscous material was added and 10 mL of ethyl acetate was added. Heat to 70 ~ 75 C dissolved, slowly dropped to 0 ~ 10 C, stirring 1 ~ 2h, precipitation of a white solid, continue stirring 3 ~ 4h, filtration, with 3mL water filter cake, filter cake drying,Obtained product 2.4g, purity 97.3%.Combined, the purity was 98.1%, the total yield was 65.3%, the ignition residue was 0.08%, and the chiral purity was 99.7%.
In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles. 154127-42-1, other downstream synthetic routes, hurry up and to see.
Reference£º
Patent; Shandong Weizhi Pharmaceutical Co., Ltd.; Shanghai Weizhi Pharmaceutical Technology Co., Ltd.; Wang Jianhua; He Yigang; Wei Yanjun; Xing Yanping; Zhao Tianchang; (27 pag.)CN107759618; (2018); A;,
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