1-BOC-3-(METHOXY)AZETIDINE

To a solution of 3-hydroxy-azetidine-1 -carboxylic acid tert-butyl ester (0.8 g, 4.62 mmol) in THF (50 mL) was added sodium hydride (60percent in mineral oil) (0.74 g, 18.5 mmol). The solution was stirred at 0 °C for 0.5 hour, followed by addition of iodomethane (2.8 mL, 46.2 mmol). The reaction mixture was stirred at room temperature overnight. The reaction was quenched with water (50 ml), and extracted with EtOAc (30 mL (1) 1-t-Butoxycarbonyl-3-methoxyazetidine [1493] A solution of 1-benzhydryl-3-hydroxyazetidine (10.0 g, 41.8 mmol) in methanol (300 ml) was subjected to catalytic hydrogenation in the presence of 10percent palladium (10.0 g) on charcoal at room temperature for 3 hours. After checking the completion of the reaction, the reaction mixture was filtered in order to remove the catalyst. To the filtrate was added di-t-butoxycarbonic anhydride (18.2 g, 83.6 mmol), and the reaction mixture was stirred at room temperature for 1 hour. After checking the completion of the reaction, the reaction mixture was concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (1:1-->1:2) as the eluant to afford 1-t-butoxycarbonyl-3-hydroxyazetidine (7.05 g, yield 97percent). [1494] Subsequently, to a solution of 1-t-butoxycarbonyl-3-hydroxyazetidine (2.5 g, 14.4 mmol) in dimethylformamide (125 ml) was added sodium hydride (55percent oil dispersion) in an ice bath. After stirring the mixture for 10 minutes in the ice bath, the resulting mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added methyl iodide (1.79 ml, 28. mmol) in an ice bath. After stirring the mixture in an ice bath for 10 minutes, the reaction mixture was stirred at room temperature for 1 hour. After checking the completion of the reaction, 10percent aqueous acetic acid solution was added thereto in an ice bath and the reaction mixture was stirred in the ice bath for 30 minutes. The reaction mixture was partitioned between ethyl acetate and 10percent aqueous sodium chloride solution. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (2:1) as the eluant to afford 1-t-butoxycarbonyl-3-methoxyazetidine (2.18 g, yield 81percent) as a colorless oil. [1495] 1H-NMR (400 MHz, CDCl3): δ (ppm) 4.16-4.10 (1H, m), 4.09-4.03 (2H, m), 3.82 (2H, dd, J=10.2, 4.4 Hz), 3.28 (3H, s), 1.44 (9H, s).A suspension of sodium hydride (2.89 g) in tetrahydrofuran (50 ml) was stirred with cooling in an ice bath. A solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (5.00 g) in tetrahydrofuran (50 ml) was gradually added, followed by stirring at the same temperature for 30 minutes. Then, the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was stirred with cooling in an ice bath again for 15 minutes. Iodomethane (3.09 ml) was added dropwise to the reaction mixture, followed by stirring for 2 hours. Water was gradually added to the reaction mixture. When bubbling stopped, the organic layer was separated. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=3:1, 2:1, 1:1, then ethyl acetate). The fractions containing the target compound were concentrated to give the title compound (1.80 g, 33.3percent) as a colorless oil. The fractions containing the starting material were concentrated and collected (2.10 g, 42.0percent).(Production Example 92) tert-Butyl 3-methoxyazetidine-1-carboxylate

Molecular Weight:187.24
XLogP3:0.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:187.12084340
Monoisotopic Mass:187.12084340
Topological Polar Surface Area:38.8
Heavy Atom Count:13
Complexity:192
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes