Application of 51419-59-1, These common heterocyclic compound, 51419-59-1, name is p-Tolylmethanesulfonyl chloride, 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.
No. B1-152: N-(1?-Methyl-2?-oxo-1?,2?-dihydrospiro[cyclobutane-1,3?-indol]-5-yl)-1-(4-methylphenyl)methanesulfonamide (0136) (0137) In a round-bottom flask which had been dried by heating, and under argon, 1-methyl-1,3-dihydro-2H-indol-2-one (1.00 g, 7 mmol) and 1,3-dibromopropane (2.06 g, 10 mmol) were dissolved in abs. N,N-dimethylformamide, and the mixture was stirred at room temperature for 5 min. The reaction solution was then cooled to 0° C., and sodium hydride (0.82 g, 20 mmol, 60percent strength dispersion) was then added a little at a time. The resulting reaction mixture was stirred for about 2 h, methanol (4 ml) was then added and after a further 5 min sat. ammonium chloride solution (15 ml) and water (200 ml) were added. The aqueous phase was extracted intensively with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification of the resulting crude product by column chromatography (gradient ethyl acetate/heptane) gave 1?-methylspiro[cyclobutane-1,3?-indol]-2?(1?H)-one (360 mg, 29percent of theory). 1H-NMR (400 MHz, CDCl3 delta, ppm) 7.52 (d, 1H), 7.27 (m, 1H), 7.09 (m, 1H), 6.77 (d, 1H), 3.20 (s, 3H), 2.67 (m, 2H), 2.33 (m, 4H). 1?-Methylspiro[cyclobutane-1,3?-indol]-2?(1?H)-one (360 mg, 1.92 mmol) was added to conc. acetic acid (5 ml), and fuming nitric acid (0.21 ml, 5.06 mmol) was then added carefully. The resulting reaction mixture was stirred at room temperature for 2 h and then diluted with ice-water. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification of the resulting crude product by column chromatography (gradient ethyl acetate/heptane) gave 1?-methyl-5?-nitrospiro[cyclobutane-1,3?-indol]-2?(1?H)-one (380 mg, 85percent of theory) as a colorless solid. 1H-NMR (400 MHz, CDCl3 delta, ppm) 8.38 (d, 1H), 8.26 (dd, 1H), 6.86 (d, 1H), 3.25 (s, 3H), 2.70 (m, 2H), 2.42 (m, 4H). In the next step, 1?-methyl-5-nitrospiro[cyclobutane-1,3?-indol]-2?(1?H)-one (450 mg, 1.55 mmol) and tin(II) chloride dihydrate (1.40 g, 6.20 mmol) were added together to abs. ethanol and stirred under argon at a temperature of 80° C. for 5 h. After cooling to room temperature, the reaction mixture was poured into ice-water and then adjusted to pH 12 using aqueous NaOH. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification of the resulting crude product by column chromatography (gradient ethyl acetate/heptane) gave 5?-amino-1?-methylspiro[cyclobutane-1,3?-indol]-2?(1?H)-one (230 mg, 66percent of theory) as a colorless solid. 1H-NMR (400 MHz, CDCl3 delta, ppm) 6.98 (d, 1H), 6.62 (m, 2H), 3.14 (s, 3H), 2.64 (m, 2H), 2.38-2.20 (m, 4H). Under argon, 5?-amino-1?-methylspiro[cyclobutane-1,3?-indol]-2?(1?H)-one (150 mg, 0.79 mmol) and (4-methylphenyl)methanesulfonyl chloride (156 mg, 0.76 mmol) were dissolved in abs. acetonitrile (5 ml) in a round-bottom flask which had been dried by heating, pyridine (0.11 ml, 1.38 mmol) and dimethyl sulfoxide (0.03 ml, 0.42 mmol) were then added and the mixture was stirred at room temperature for 6 h. The reaction mixture was then concentrated under reduced pressure, water, dil. hydrochloric acid and dichloromethane were added to the residue that remained and the aqueous phase was extracted repeatedly with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification of the resulting crude product by column chromatography (gradient ethyl acetate/heptane) gave N-(1?-methyl-2?-oxo-1?,2?-dihydrospiro[cyclobutane-1,3?-indol]-5?-yl)-1-(4-methylphenyl)methanesulfonamide (118 mg, 46percent of theory) as a colorless solid. 1H-NMR (400 MHz, CDCl3 delta, ppm) 7.29 (m, 3H), 7.16 (d, 1H), 6.96 (br. s, 1H, NH), 6.61 (d, 1H), 4.30 (s, 2H), 3.13 (s, 3H), 2.62 (m, 2H), 2.33 (s, 3H), 2.32-2.17 (m, 4H).
The synthetic route of 51419-59-1 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; BAYER CROPSCIENCE AKTIENGESELLSCHAFT; FRACKENPOHL, Jens; BOJACK, GUIDO; HELMKE, HENDRIK; LEHR, STEFAN; MUELLER, THOMAS; WILLMS, LOTHAR; DITTGEN, JAN; SCHMUTZLER, DIRK; BICKERS, UDO; STREK, HARRY; BALTZ, RACHEL; (88 pag.)US2016/237035; (2016); A1;,
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