Application of 2106-04-9, A common heterocyclic compound, 2106-04-9, name is 3-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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.
Step 1: 5-Bromo-N-(3-chloro-2-fluorophenyl)pyridin-3-amineA 20 mL microwave vial was charged with 3-chloro-2-fluoroaniline (473 jiL, 4.22 mmol) and diluted with 1,4-dioxane (16.9 mL). To that solution was added 3,5- dibromopyridine (1000 mg, 4.22 mmol), sodium tert-butoxide (568 mg, 5.91 mmol),xantphos (48.9 mg, 0.0840 mmol), and tris(dibenzylideneacetone)dipalladium(0) (38.7 mg, 0.0420 mmol). The vial was sealed and degassed using ultra pure argon and sonication for 1 mm. The vial was placed into a reaction block preheated to 80 C. After 1 h, the contents of the vial were transferred to a flask, and the volatiles were concentrated under reduced pressure. The resulting brown solids were dissolved with ethyl acetate andwater. The contents of the flask were transferred into a separatory funnel where the layers were separated. The organic was washed with water and brine, dried over magnesium sulfate, and purified by silica gel flash chromatography. Upon dissolving the sample with DCM, a white solid persisted, which was collected by filtration and washed with hexanes to give 541 mg of desired product. The supernatant was concentrated under reducedpressure and purified by silica gel column chromatography (24 g ISCO RediSep Rf, loaded inlwith: DCM and dried, initial waste: 0 mL, fraction size: 9 mL 13x 100 mm, and eluted with ethyl acetate in dichloromethane 0% [75 mL], 0-5% [201 mL], 5% [300 mL]).The fractions were collected and combined with the previously collected solids to give 921 mg(72%). ?H NMR (400MHz, CDC13)oe 8.35 (d,J=2.5 Hz, 1H), 8.31 (d,J1.8 Hz, 1H), 7.58 (t,J=2.1 Hz, 1H), 7.22-7.14 (m, 1H), 7.08-7.01 (m, 2H), 5.86 (br. s., 1H). Mass found 302 [M+H] .
The synthetic route of 2106-04-9 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; NORRIS, Derek J.; DELUCCA, George V.; GAVAI, Ashvinikumar V.; QUESNELLE, Claude A.; GILL, Patrice; O’MALLEY, Daniel; VACCARO, Wayne; LEE, Francis Y.; DEBENEDETTO, Mikkel V.; DEGNAN, Andrew P.; FANG, Haiquan; HILL, Matthew D.; HUANG, Hong; SCHMITZ, William D.; STARRETT, JR, John E.; HAN, Wen-Ching; TOKARSKI, John S.; MANDAL, Sunil Kumar; WO2015/100282; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics