[(2S)-azetidin-2-yl]methanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Said solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (0.88 g, 10.5 mmol) was then added, and benzyloxycarbonyl chloride (1.76 g, 10.3 mmol) was added thereto at room temperature, followed by 14 hours of stirring. The solution was adjusted to pH 7 and extracted with ethyl acetate (50 mL ×2), the extract was washed with water (50 mL×1), dried over magnesium sulfate and filtered, and the filtrate was concentrated. The concentrate was subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate (1/1) as a mobile phase for separation/purification, to give (S)-N-benzyloxycarbonylazetidine-2-methanol (0.781 g, yield 75%) as a pale yellow oil. (S)-2-N-benzyloxycarbonyl-1,4-butanediol was obtained as a byproduct (0.096 g, yield 9%). was then added extracted with ethyl acetate (50 mL ×2) the extract was washed with water (50 mL×1) dried over magnesium sulfate filtered the filtrate was concentrated for separation/purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Said solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (0.44 g, 5.29 mmol) was then added, and benzyloxycarbonyl chloride (0.88 g, 5.16 mmol) was added thereto at room temperature, followed by 14 hours of stirring. The solution was adjusted to pH 7 and extracted with ethyl acetate (50 mL ×2), the extract was washed with water (50 mL×1), dried over magnesium sulfate and filtered, and the filtrate was concentrated. The concentrate was subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate (1/1) as a mobile phase for separation/purification, to give (S)-N-benzyloxycarbonylazetidine-2-methanol (0.499 g, yield 96%) as a pale yellow oil. (S)-2-N-benzyloxycarbonyl-1,4-butanediol was obtained as a byproduct (0.032 g, yield 6%). was then added extracted with ethyl acetate (50 mL ×2) the extract was washed with water (50 mL×1) dried over magnesium sulfate filtered the filtrate was concentrated for separation/purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Said solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (0.873 g, 10.5 mmol) was then added and benzyloxycarbonyl chloride (1.75 g, 10.5 mmol) was added at room temperature. Thereafter, stirring was continued for 14 hours. The reaction mixture was adjusted to pH 7 and extracted with ethyl acetate (50 mL×2), the extract was washed with water (50 mL×1), dried over magnesium sulfate and filtered, and the filtrate was concentrated. The concentrate was subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate as a mobile phase for separation/purification, to give (S)-N-benzyloxycarbonylazetidine-2-methanol as a pale yellow oil (0.495 g, yield 49%). As a byproduct, (S)-2-N-benzyloxycarbonyl-1,4-butanediol was obtained (0.26 g, yield 24%). was then added extracted with ethyl acetate (50 mL×2) the extract was washed with water (50 mL×1) dried over magnesium sulfate filtered the filtrate was concentrated for separation/purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (2.00 g, 24.0 mmol) was then added, and benzyloxycarbonyl chloride (4.00 g, 24.0 mmol) was added at room temperature. Thereafter, stirring was continued for 14 hours. The reaction mixture was adjusted to pH 7 and extracted with ethyl acetate (50 mL×2), and the extract was washed with water (50 mL×1), dried over magnesium sulfate and filtered. The filtrate was concentrated and subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate (1/1) as a mobile phase for separation/purification, to give (S)-N-benzyloxycarbonylazetidine-2-methanol (2.14 g, yield 97.0%). The yield was improved as compared with that obtained in Example 1 (69.1%). The formation of the byproduct (S)-2-N-benzyloxycarbonyl-1,4-butanediol decreased to a yield of 2.5% (0.06 g). was then added extracted with ethyl acetate (50 mL×2) the extract was washed with water (50 mL×1) dried over magnesium sulfate filtered The filtrate was concentrated for separation/purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (2.00 g, 24.0 mmol) was then added, and benzyloxycarbonyl chloride (4.00 g, 24.0 mmol) was added thereto at room temperature. The mixture was then stirred for 14 hours. The solution was adjusted to pH 7, and extracted with ethyl acetate (50 mL×2). The extract was washed with water (50 mL×1), dried over magnesium sulfate and filtered, and the filtrate was concentrated. The concentrate was subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate (1/1) as a mobile phase. This separation/purification gave (S)-N-benzyloxycarbonylazetidine-2-methanol (1.88 g, yield 85.0%). The yield was improved as compared with that obtained in Example 1 (69.1%). The formation of the byproduct (S)-2-N-benzyloxycarbonyl-1,4-butanediol decreased to a yield of 3.0% (0.07 g). was then added at room temperature extracted with ethyl acetate (50 mL×2) The extract was washed with water (50 mL×1) dried over magnesium sulfate filtered the filtrate was concentrated This separation/purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (2.00 g, 24.0 mmol) was then added, and benzyloxycarbonyl chloride (4.00 g, 24.0 mmol) was added thereto at room temperature. The mixture was then stirred for 14 hours. The solution was adjusted to pH 7, and extracted with ethyl acetate (50 mL×2). The extract was washed with water (50 mL×1), dried over magnesium sulfate and filtered, and the filtrate was concentrated. The concentrate was subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate (1/1) as a mobile phase. This separation/purification gave (S)-N-benzyloxycarbonylazetidine-2-methanol (2.01 g, yield 91.0%). The yield was improved as compared with that obtained in Example 1 (69.1%). The formation of the byproduct (S)-2-N-benzyloxycarbonyl-1,4-butanediol decreased to a yield of 7.0% (0.17 g). was then added at room temperature extracted with ethyl acetate (50 mL×2) The extract was washed with water (50 mL×1) dried over magnesium sulfate filtered the filtrate was concentrated This separation/purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Said solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (2.00 g, 24.0 mmol) was then added and benzyloxycarbonyl chloride (ZCl) (4.00 g, 24.0mmol) was added at room temperature. Thereafter, stirring was continued for 14 hours. The mixture was adjusted to pH 7 and extracted with ethyl acetate (50 mL ×1), the extract was washed with water (50 mL×1) and dried over magnesium sulfate and, after filtering off the same, the filtrate was concentrated. This was subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate (1/1) as a mobile phase for separation and purification, whereby a pale yellow oil was obtained (1.50 g). Based on its proton NMR spectrum (FIG. 3), this was identified as the desired product (S)-N-benzyloxycarbonylazetidine-2-methanol (yield 69.1%). Further, as a byproduct, there was obtained (S)-2-N-benzyloxycarbonyl-1,4-butanediol (0.27 g, yield 11.4%). Its proton NMR spectrum is shown in FIG. 4. was then added extracted with ethyl acetate (50 mL ×1) the extract was washed with water (50 mL×1) dried over magnesium sulfate after filtering off the same, the filtrate was concentrated for separation and purification, whereby a pale yellow oil was obtained (1.50 g)