N-Benzyl-3-hydroxyazetidine

Preparation Example 37: l-benzyl-azetidine-3-oll-Benzyl-3-trimethylsilyloxy-azetidine (1.8 g, 7.65 mmol) prepared in Preparation Example 25 was dissolved in methanol (9 ml), sodium methoxide (826 mg, 15.29 mmol) was added thereto, and stirred at room temperature for 30 min. The solvent was removed by evaporation under a reduced pressure, and the residue was extracted using ethyl acetate. The organic extract layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under a reduced pressure, to obtain 0.964 g (yield: 77 percent) of the title compound.*H NMR (200 MHz, CDC130.0 grams of benzylamine and 450 ml of process water were added to a 1000 ml four-necked flask, slowly cooled to 0 to 5 ° C, controlled temperature at 0 to 5 ° C, slowly dripped through a constant pressure dropping funnel 30.0 g of propylene oxide, after the end of the dropwise addition, stirring was continued at 0 to 5 ° C for 16 hours, the sample was confirmed by TLC to be finished, filtered, washed with 60 ml of process water, and the filter cake was placed in a vacuum drying oven, and Controlling the temperature to dry below 50 ° C gives 40 grams of intermediate compound of intermediate 11. Under nitrogen protection, 40 g of the intermediate compound obtained above and 485 ml of acetonitrile were added to a 1000 ml four-necked flask, the temperature was controlled below 30 ° C, and 42 g of sodium carbonate was added to the reaction bottle in batches. After the completion of the addition, the temperature was raised to 80 to 90 ° C, and the mixture was stirred under reflux for 16 hours. The reaction was confirmed by TLC, and the solvent was concentrated and evaporated to give a viscous white solid. The above viscous white solid was dissolved in 180 ml of methyl tert-butyl ether, and a solution of oxalic acid (28 g) methyl t-butyl ether (140 ml) was slowly added dropwise under stirring to adjust the temperature to 20~ Stirring at 25 ° C for 2 to 3 hours, filtration; adding filter cake and 300 ml of ethyl acetate to a 1000 ml four-necked flask, slowly adding 150 ml of 10percent sodium carbonate solution, layering, and concentrating the organic phase to obtain 39.6 g. A colorless oily product with a yield of 88.7percent.(b) Add in 2L reaction bottle30.0 grams of benzylamine and 450 ml of process water were added to a 1000 ml four-necked flask, slowly cooled to 0 to 5 C, controlled temperature at 0 to 5 C, slowly dripped through a constant pressure dropping funnel 30.0 g of propylene oxide, after the end of the dropwise addition, stirring was continued at 0 to 5 C for 16 hours, the sample was confirmed by TLC to be finished, filtered, washed with 60 ml of process water, and the filter cake was placed in a vacuum drying oven, and Controlling the temperature to dry below 50 C gives 40 grams of intermediate compound of intermediate 11. Under nitrogen protection, 40 g of the intermediate compound obtained above and 485 ml of acetonitrile were added to a 1000 ml four-necked flask, the temperature was controlled below 30 C, and 42 g of sodium carbonate was added to the reaction bottle in batches. After the completion of the addition, the temperature was raised to 80 to 90 C, and the mixture was stirred under reflux for 16 hours. The reaction was confirmed by TLC, and the solvent was concentrated and evaporated to give a viscous white solid. The above viscous white solid was dissolved in 180 ml of methyl tert-butyl ether, and a solution of oxalic acid (28 g) methyl t-butyl ether (140 ml) was slowly added dropwise under stirring to adjust the temperature to 20~ Stirring at 25 C for 2 to 3 hours, filtration; adding filter cake and 300 ml of ethyl acetate to a 1000 ml four-necked flask, slowly adding 150 ml of 10% sodium carbonate solution, layering, and concentrating the organic phase to obtain 39.6 g. A colorless oily product with a yield of 88.7%.General procedure: 6-chloronicotinate (2 mmol) and amine 5a-5g (3 mmol) were added to amicrowave vial (10 ml) equipped with a stir bar. NMP (3 mL) was then addedfollowed by triethylamine (6 mmol). The vial was sealed and irradiated in themicrowave at 180 C (high absorption) for 60 min. The mixture was then dilutedwith H2O (10 mL) and extracted with EtOAc (3 × 15 mL). The combinedorganic layers were dried over MgSO4 and concentrated. The residuewas purified by flash chromatography on silica gel using ethylacetate-petroleum ether gradient elution (1:4 - 1:2, v/v) to afford the titlecompound 7a-7g.

Molecular Weight:163.22
XLogP3:0.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:163.099714038
Monoisotopic Mass:163.099714038
Topological Polar Surface Area:23.5
Heavy Atom Count:12
Complexity:137
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes