106614-28-2, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 106614-28-2 as follows.
To a 50 mL round bottom flask purged with and maintained 1..mder an inertatmosphere of nitrogen v.¡¤as added (1 S,4S,5R)-5-[[5-cyclopropyl-3-(2,6-dichloropheny l)- L2-oxazol-4-yl]rnethoxy]-2-azabicyclo[2.2.1]heptane hydroiodide salt l2dd (250 rng, 0.49 mmol, 1.00 equiv.), methyl2,4-dit1uorobenzoate (225 mg, 1.31 mmol, 2.67 equiv.), CsF (298rng, 196 mmol, 4.00 equiv.), and 1-Ethyl-3-methylimidazoliurn dimethyl phosphate (3 mL)The resulting mixture was heated at 90C overnight After cooling to room temperature, themixtme wa;;; diluted with 20 mL off-hO and extracted with ethyl acetate (30 mL x 2). The5 cornbined organic extracts were washed with brine (30 mL x 3), dried over anhydrous sodiumsulfate and concentrated under vacuum. The residue was purified by silica gel columnchromatography eluting ~ith ethyl acetate/petroleum ether (I: 3). Removal of solventsafforded methy 14-[(1 S,4S,5R)-5-[[5-cydopropyl-3-(2,6-dichloropheny 1)-1,2-oxazol-4-y l]methoxy]-2-azabicyclo[2.2.l ]hepi:m-2-yl]-2-fluorobenzoate T-177 (158 6 mg, 50%) as an10 off-white solid. 1H-NMR (300 MHz, CDCb): 8 7.77 (t, J = 8.7 Hz, lH), 7.49-7.29 (m 3H),6.22 (dd, J ” 8.8, 2.4 Hz, 1H), 6.10 (dd, J ” 14.3, 2.3 Hz, 1H), 4.28 (s, 2H), 4.04 (s, lH), 3.87(s, 3H), 3.54- 3.44 (m, H-T), 3.35 (dd, J ‘” 9.3, 4.0 Hz, 1H), 2.63- 2.49 (m, 2H), 2.12 (ddt, J= 12.9, 9.6, 4.8 Hz, lH), l 85 (ddd, J = 13.3, 6.8, 2.4 Hz, IH), 1.71 – 1..54 (m, 2H), 1.41-1.22 (m, 3H), 1.27–1.03 (m, 2H): MS (ES, mlz): [M+1] = 531.05.
According to the analysis of related databases, Methyl 2,4-difluorobenzoate, the application of this compound in the production field has become more and more popular.
Reference:
Patent; ARDELYX, INC.; CHAO, Jianhua; JAIN, Rakesh; HU, Lily; LEWIS, Jason Gustaf; BARIBAULT, Helene; CALDWELL, Jeremy; (582 pag.)WO2018/39386; (2018); A1;,
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