Synthetic Route of 33420-52-9 ,Some common heterocyclic compound, 33420-52-9, molecular formula is C3H6F2O, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
To tert-butyl 4-(1-(4-(methoxycarbonyl)-3-methylthiophen-2-yl)propylidene)piperidine-1-carboxylate (12.1 g, 31.9 mmol) was added HC1 in dioxane (30 mL, 120 mmol). After stirring for 30 min the reaction was evaporated to dryness to give the crude amine hydrochloride salt as a white solid foam. To a stirred solution of 2,2-difluoropropan-l-ol (16.3 g, 170 mmol) and pyridine (16.3 mL, 202 mmol) in CH3CN (250 mL) at 0 C in an ice bath was added dropwise Tf20 (28 mL, 166 mmol). The reaction was stirred for 30 min at 0 C, then added cold to a slurry of the above amine hydrochloride and K2C03 (46.8 g, 339 mmol) in CH3CN (100 mL). The reaction was rinsed down with CH3CN (50 mL). The reaction was allowed to warm to RT, heated to 50 C and stirred for 6 h. The reaction was evaporated to dryness under vacuum, taken up in DCM, washed with water, brine, dried (Na2S04), filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography (Isco RediSep Rf Gold 120g, 5 to 15% EtOAc in hexanes). The pure fractions were combined and evaporated to dryness under vacuum to give methyl 5-(1-(1-(2,2- difluoropropyl)piperidin-4-ylidene)propyl)-4-methylthiophene-3 -carboxylate ( 10.05 g, 24.74 mmol, 78 % yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) delta 8.03 (s, 1H), 3.86 (s, 3H), 2.70 (t, J=12.6 Hz, 4H), 2.57 – 2.43 (m, 4H), 2.32 (br. s., 2H), 2.25 (s, 3H), 2.06 (br. s., 2H), 1.67 (t, J=18.8 Hz, 3H), 0.94 (t, J=7.5 Hz, 3H). MS(ES) [M+H]+ 358.2.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,33420-52-9, its application will become more common.
Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; KNIGHT, Steven David; NEWLANDER, Kenneth Allen; TIAN, Xinrong; (112 pag.)WO2016/66697; (2016); A1;,
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