1-(苯基甲基)-2-氮杂环丁烷甲酸乙酯

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 77 g of water were added 0.5 g of the immobilized enzyme produced in Example 1 above and 65 g of ethyl N-benzylazetidine-2-carboxylate, followed by stirring at 10° C. for 10 hours. To the reaction mixture, were added 65 g of methylisobutyl ketone and 36 g of ethanol, and further stirring was conducted for 30 minutes. The reaction mixture was thereafter filtrated, and the filtrate was subjected to separation. To the aqueous layer were added 65 g of methylisobutyl ketone and 6.5 g of ethanol followed by stirring for 30 minutes and the separation. This operation was repeated twice. Thus resulting aqueous layer was concentrated under a reduced pressure (10 kPa or lower) to give 60 g of crude (S)-N-benzylazetidine-2-carboxylic acid (43 weight %). produced in Example 1 above further stirring was conducted for 30 minutes The reaction mixture was thereafter filtrated the filtrate was subjected to separation To the aqueous layer were added 65 g of methylisobutyl ketone and 6.5 g of ethanol by stirring for 30 minutes the separation Thus resulting aqueous layer was concentrated under a reduced pressure (10 kPa or lower)

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 10.0 g of N-Benzylazetidine-2-carboxylic acid ethyl ester, 29.6 g of t-butyl methyl ether and 26.7 g of water are mixed at 20 to 25° C. and then 0.333 g of Enzyme (Chirazyme L-2) was added thereto and the resulting solution was heated to 40° C. and stirred for 7 hours. Settled solution was separated into an aqueous phase and an organic phase. The aqueous phase was washed twice with t-butyl methyl ether to yield an aqueous solution of optically active N-benzylazetidine-2-carboxylic acid and a combined organic phase of N-benzylazetidine-2-carboxylic acid ethyl ester. Results of the same analysis as in the Example 1 is shown in Table 8. 0.333 g of Enzyme (Chirazyme L-2) was added Settled solution was separated into an aqueous phase The aqueous phase was washed twice with t-butyl methyl ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (Wasserman, H. H. et al. J Org. Chem. 1981, 46(15), 2991-2999). A mixture of (±)ethyl 2,4-dibromobutanoate (39) (15 g, 54.8 mmol), triethylamine (16.6 g, 164 mmol) and benzylamine (5.87 g, 54.8 mmol) was heated to reflux for 3 hours then concentrated under reduced pressure to give a solid suspension. Water (150 ml) was then added and the mixture extracted with ether (2×100 ml). The organic phase was dried and then concentrated under reduced pressure and the residue purified by dry flash chromatography on silica (hexanes then 1:3 ethyl acetate/hexanes) to give 40 as a pale yellow oil (6.3 g, 53%); 1H NMR (300 MHz, CDCl3) δ 7.37-7.27 (m, 5H), 4.16-4.03 (m, 2H), 3.82 (d, J=12.6 Hz, 1H), 3.73 (dd, J=8.4, 8.4 Hz, 1H), 3.61 (d, J=12.8 Hz, 1H), 3.34 (ddd, J=7.4, 7.4, 2.0 Hz, 1H), 2.95 (ddd, J=7.4, 7.4, 7.4 Hz, 1H), 2.44-2.31 (m, 1H), 2.27-2.16 (m, 1H), 1.20 (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 172.5, 137.1, 129.0, 128.7, 128.2, 127.1, 64.5, 62.4, 60.5, 50.8, 21.5, 14.0. was heated to reflux for 3 hours then concentrated under reduced pressure to give a solid suspension the mixture extracted with ether (2×100 ml) The organic phase was dried concentrated under reduced pressure the residue purified by dry flash chromatography on silica (hexanes

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 10.0 g of N-Benzylazetidine-2-carboxylic acid ethyl ester, 29.6 g of t-butyl methyl ether and 26.7 g of water are mixed at 20 to 25° C. and then 0.333 g of Enzyme (Chirazyme L-2) was added thereto and the resulting solution was heated to 40° C. and stirred for 7 hours. Settled solution was separated into an aqueous phase and an organic phase. The aqueous phase was washed twice with t-butyl methyl ether to yield an aqueous solution of optically active N-benzylazetidine-2-carboxylic acid and a combined organic phase of N-benzylazetidine-2-carboxylic acid ethyl ester. Results of the same analysis as in the Example 1 is shown in Table 8. 0.333 g of Enzyme (Chirazyme L-2) was added Settled solution was separated into an aqueous phase The aqueous phase was washed twice with t-butyl methyl ether

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 77 g of water were added 0.5 g of the immobilized enzyme produced in Example 1 above and 65 g of ethyl N-benzylazetidine-2-carboxylate, followed by stirring at 10° C. for 10 hours. To the reaction mixture, were added 65 g of methylisobutyl ketone and 36 g of ethanol, and further stirring was conducted for 30 minutes. The reaction mixture was thereafter filtrated, and the filtrate was subjected to separation. To the aqueous layer were added 65 g of methylisobutyl ketone and 6.5 g of ethanol followed by stirring for 30 minutes and the separation. This operation was repeated twice. Thus resulting aqueous layer was concentrated under a reduced pressure (10 kPa or lower) to give 60 g of crude (S)-N-benzylazetidine-2-carboxylic acid (43 weight %). produced in Example 1 above further stirring was conducted for 30 minutes The reaction mixture was thereafter filtrated the filtrate was subjected to separation To the aqueous layer were added 65 g of methylisobutyl ketone and 6.5 g of ethanol by stirring for 30 minutes the separation Thus resulting aqueous layer was concentrated under a reduced pressure (10 kPa or lower)