As the paragraph descriping shows that 101691-65-0 is playing an increasingly important role.
With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.101691-65-0,(Tetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonate,as a common compound, the synthetic route is as follows.
[0217] A solution of (tetrahydro-pyran-4-yl)-methanol (1.0 g, 8.61 mmol, prepared according to WO 99/00385) in methylene chloride (30 mL) at 25 C. was treated with 4-(dimethylamino)pyridine (1.17 g, 9.47 mmol) and p-toluenesulfonyl chloride (1.64 g, 8.61 mmol) and then was allowed to stir at 25 C. overnight. The reaction was then transferred to a separatory funnel and washed with a 1N aqueous hydrochloric acid solution (10 mL), a saturated aqueous sodium bicarbonate solution (10 mL), and a saturated aqueous sodium chloride solution (10 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 75/25 hexanes/ethyl acetate) afforded toluene-4-sulfonic acid tetrahydro-pyran-4-yl methyl ester (1.77 g, 76%) as a colorless oil. [0218] A solution of toluene-4-sulfonic acid tetrahydro-pyran-4-yl methyl ester (1.77 g, 6.55 mmol) and sodium iodide (2.85 g, 18.99 mmol) in acetone (26 mL) was heated to 60 C. for 16 h. The resulting suspension was then cooled to 10 C. and filtered. The salts were rinsed with cold acetone (5 mL), and the filtrate and washings were concentrated in vacuo to a thick slurry. This slurry was treated with methylene chloride (10 mL). The resulting precipitate was removed by filtration and was washed with methylene chloride (10 mL). The filtrate and washings were then dried over magnesium sulfate, filtered through a pad of silica gel, and then concentrated in vacuo to afford 4-iodomethyl-tetrahydro-pyran as a light yellow oil. [0219] A solution of diisopropylamine (0.33 mL, 2.38 mmol) in tetrahydrofuran (6 mL) cooled to -78 C. under an argon atmosphere was treated with a 2.5M solution of n-butyllithium in hexanes (0.95 mL, 2.38 mmol). The reaction mixture was stirred at -78 C. for 15 min, after which time, a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (prepared as in Example 4, 500 mg, 2.17 mmol) in tetrahydrofuran (1 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.5 mL) was slowly added via a cannula. The greenish yellow solution was allowed to stir at -78 C. for 1 h, after which time, a solution of 4-iodomethyl-tetrahydro-pyran (588 mg, 2.60 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.5 mL) was added via a cannula. The reaction mixture was then allowed to warm to 25 C., where it was stirred for 16 h. The reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (30 mL). This solution was extracted with ethyl acetate (3¡Á20 mL). The combined organic layers were washed with a 10% aqueous sulfuric acid solution (2¡Á50 mL) and a saturated aqueous sodium bicarbonate solution (2¡Á50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 75/25 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid methyl ester (431 mg, 61%) as a yellow oil: EI-HRMS m/e calcd for C16H21ClO3S (M+) 328.0900, found 328.0898. [0220] A solution of 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid methyl ester (200 mg, 0.61 mmol) in formic acid (0.23 mL) and tetrahydrofuran (0.5 mL) cooled to 0 C. was treated with a 30% aqueous hydrogen peroxide solution (0.35 mL, 3.04 mmol). The reaction was slowly warmed to 25 C. where it was stirred for 16 h. The reaction mixture was then cooled to 0 C., quenched with a saturated aqueous sodium sulfite solution, and then extracted with ethyl acetate (3¡Á20 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 60/40 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid methyl ester (190 mg, 87%) as a colorless oil: (ES)+-HRMS m/e calcd for C16H21ClO5S (M+Na)+ 383.0690, found 383.0692. [0221] A
As the paragraph descriping shows that 101691-65-0 is playing an increasingly important role.
Reference£º
Patent; Corbett, Wendy Lea; Grimsby, Joseph Samuel; Haynes, Nancy-Ellen; Kester, Robert Francis; Mahaney, Paige Erin; Racha, Jagdish Kumar; Sarabu, Ramakanth; Wang, Ka; US2003/225283; (2003); A1;,
Tetrahydropyran – Wikipedia
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