Pyridinium p-toluenesulfonate

white to light beige crystalline powder or

To the reactor was added p-toluenesulfonic acid (5 g, 0.029 mol), dry tetrahydrofuran (40 mL) was added under nitrogen, and the reaction was carried out at room temperature.The reaction solution was cooled to 0 to 5 ° C, and pyridine (2.75 g, 0.035 mol) was added dropwise to the solution at that temperature, and the mixture was added over 20 to 30 minutes and stirred for 30 minutes.The reaction was filtered in a nitrogen atmosphere and the resulting filter cake was washed with 5 mL of dry tetrahydrofuran and the wet cake was dried in a vacuum oven at 45-50 ° C for 4 hours to give pyridinium 4-methylbenzenesulfonate.As shown in Figs. 7 to 11, the yield of pyridinium 4-methylbenzenesulfonate was 6 g, the yield was 82.19percent, and the purity was 100percent by HPLC.(2) To the reactor was added p-toluenesulfonic acid (5 g, 0.029 mol)Dry tetrahydrofuran (40 mL) was added under nitrogen conditions, Reaction at room temperature;The reaction solution was cooled to 0 to 5 ° C, To the solution was added pyridine (2.75 g, 0.035 mol) dropwise at this temperature, In 20 to 30 minutes plus finished, Stir for 30 minutes;The reaction was filtered in a nitrogen atmosphere, The resulting filter cake was washed with 5 mL of dry tetrahydrofuran, The wet cake was dried in a vacuum oven at 45 to 50 ° C for 4 hours to give pyridinium 4-methylbenzenesulfonate.Paratoluenesulfonic acid (5 g, 0.029 mol) was added to the reactor, Under nitrogen protection, Continue to add tetrahydrofuran (40 mL)The reaction at room temperature; the reaction solution was cooled to 0 ~ 5 , Then, pyridine (2.75 g, 0.035 mol) was dropped into the solution, And ensure that 20 to 30 minutes drop finished, Then stirred for 30 minutes;Filter under nitrogen, The resulting filter cake was washed with 5 mL of tetrahydrofuran, It was dried in a vacuum oven at 45 to 50 ° C for 4 hours, Pyridinium 4-methylbenzenesulfonate was obtained.As shown in FIGS. 7 to 11, the resulting pyridinium 4-methylbenzenesulfonate had a mass of 6 g, Yield 82.19percent, HPLC purity 100percent.To the reactor was added p-toluenesulfonic acid (5g, 0.029mol), under nitrogen, Continue to add tetrahydrofuran (40mL), at room temperature; the reaction solution was cooled to 0 ~ 5 , and then, Pyridine (2.75 g, 0.035 mol) was added dropwise to the solution and the dropwise addition was completed within 20-30 minutes.Then stirred for 30 minutes;Filter under nitrogen and the filter cake was washed with 5 mL of tetrahydrofuran, This was dried in a vacuum oven at 45 to 50 ° C for 4 hours to obtain pyridinium 4-methylbenzenesulfonate.As shown in FIGS. 7 to 11, the obtained pyridinium 4-methylbenzenesulfonate had a mass of 6 g and a yield of 82.19percent, HPLC purity 100percent.(c) Oxidation of silylether (39) with pyridinium dichromate (PDC) gives ketone (40): CH2 Cl2, 0 C., PDC (2.7 equiv.), PPTS (pyridinium p-toluene sulphonate; trace), 1h; room temp., 4h, yield 87%. 1 H-NMR (CDCl3, delta): 0.01 (s, 6H, CH3 Si), 0.86 (s, 9H, Me3 Si), 1.02 (d, J=5.75 Hz, 3H, CH3 -21), 1.21 (s, 6H, CH3 -26, 27), 3.34 (d, J=10.8 Hz, 1H, CHHOTBS), 3.49 (d, J=11.01 Hz, 1H, CHHOTBS), 3.36 (s, 3H, OCH3), 4.70 (s, 2H, OCH2 O). 13 C-NMR (CDCl3, delta): 18.20, 19.19, 19.32, 20.25, 23.81, 25.79, 26.27, 26.37, 27.53, 35.35, 35.80, 36.39, 40.54, 42.21, 53.39, 55.03, 56.89, 60.21, 61.78, 76.27, 91.03, 211.22.Deprotection of a Compound of Formula III with PPTS To a solution of the appropriate compound III (0.16 mmol) in 99% ethanol (2 ml) PPTS (2 mg) is added, and the mixture is stirred at 50 C. under argon for one hour. Ethyl acetate (15 ml) is added and the mixturre extracted with saturated aqueous NaHCO3 (3*5 ml) and water (5 ml). The organic phase is dried and evaporated in vacuo to yield a crude product, which is purified by chromatography to give the desired compound.The (2) To the compound obtained in Production (0.88M, tetrahydrofuran solution, 7.10 ml) was added, at -10 C., copper (I) cyanide.lithium dichloride (1.0M, tetrahydrofuran solution, 7.85 ml). The mixture was stirred at the same temperature for 15 minutes. Thereto were added, at -78 C., chlorotrimethylsilane (0.72 ml) and a diethyl ether solution (12.6 ml) of the compound obtained in the above (1) (1.55 g). The mixture was heated to 0 C. in about 2hours, with stirring. To the reaction mixture was added a saturated aqueous ammonium chloride solution (50 ml), followed by extraction with hexane. The organic layer was washed with a saturated aqueous sodium chloride solution, dried and concentrated. The resulting residue was dissolved in a mixture of diethyl ether (3.2 ml), isopropanol (12.8 ml) and Then, 190 mg (1 mmol) of p-toluenesulfonic acid was added, after which 12.5 g (120 mmol) of 2, 2-dimethoxypropane was further added. The resulting mixture was stirred under nitrogen gas at room temperature for 1 hour. One hour after the start of reaction, the reaction mixture was sampled and analyzed by HPLC to confirm that the objective triol acid derivative (compound of the formula (4)) had formed in a yield of not less than 90%. This reaction mixture was neutralized with pyridine, added with water, and stirred to extract the To a mixture of the obtained Intermediate 10, 32 mL of chloroform, and 2.3 g of pyridine, 4.1 g of trifluoromethanesulfonic anhydride was added at 0 C., followed by stirring for 8 hours. To the resulting mixture was added a saturated aqueous ammonium chloride solution, and the mixture was extracted with MTBE. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain 2.7 g of an intermediate 11 represented by the following formula.DIAD (1.69 mL , 8.53 mmol) was added to a solution of 3-(benzyloxy)cyclobutanol (800 mg, 4.26 mmol), Step C: 5-Bromo-1-methoxy-1, 3-dihydro-isoindole-2-carboxylic acid tert-butyl ester To a solution of the 5-bromo-1-hydroxy-1, 3-dihydro-isoindole-2-carboxylic acid tert-butyl ester in MeOH (50 mL) was added pyridinium p-toluensulfonate (500 mg, 1.9 mmol). The reaction mixture was stirred at room temp for 2 hr and then quenched with triethylamine (2.4 g, 23.7 mmol). The reaction was concentrated in vacuo to give the title compound, which was used in the next step without further purification.

Pyridinium p-Toluenesulfate is used in the synthesis of a subdomain of the cytochrome P450 BM3 enzyme, for use in screening systems for drug candidates.

Molecular Weight:251.30
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:251.06161445
Monoisotopic Mass:251.06161445
Topological Polar Surface Area:75.6
Heavy Atom Count:17
Complexity:237
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes