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CAS No. : | 104587-62-4 | MDL No. : | MFCD10565790 |
Formula : | C4H9NO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | FTWWNKCHSPDIQW-BYPYZUCNSA-N |
M.W : | 87.12 | Pubchem ID : | 10855374 |
Synonyms : |
|
Chemical Name : | (S)-Azetidin-2-ylmethanol |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Borane tetrahydrofuran complex (1.0M solution in tetrahydrofuran,25.0 mL, 24.7 mmol) was added to a solution of L-azetidine-2-carboxtlicacid (5, 1.0 g, 9.9 mmol) in tetrahydrofuran (15.0 mL) under nitrogenatmospheric conditions. The resulting mixture was stirred for 90 minunder reflux. Afetr the reaction had cooled to room temperature, anaqueous solution of potassium hydrogen sulfate (10%, 15.0 mL) wasadded to the mixture, which was further refluxed for 15 min. Themixture was evaporated under reduced pressure to yield the residue of(S)-azetidine-2-ylmethanol. An aqueous solution of sodium hydroxide(1 M, 20.0 mL) and di-tert-butyl dicarbonate (2.4 g, 11.9 mmol) wereadded to a solution of (S)-azetidine-2-ylmethanol (862 mg, 9.9 mmol)in water (20.0 mL) and 1,4-dioxane (15.0 mL) at 0 C. The mixture wasthen stirred for 24 h at room temperature. The reaction mixture waspoured into a saturated aqueous solution of sodium bicarbonate andextracted with chloroform. The organic layer was dried over sodiumsulfate and concentrated under reduced pressure. The residue waspurified by silica gel column chromatography (n-hexane/ethylacetate=1/1) to yield (-)-6 (1.79 g, 97%) in the form of a colorless oil. | ||
With borane-THF; In tetrahydrofuran; at 90℃; for 1.5h;Inert atmosphere; | To a solution of <strong>[2133-34-8]L-azetidine-2-carboxylic acid</strong> (1.0 g, 9.9 mmol, >99% e.e.) in THF (15 mL), a borane-THF complex (1.0 M solution in THF, 25 mmoL) was added. The mixture was refluxed under a N2 stream for 1.5 hr. Potassium hydrogen sulfate (10% solution in water,15 mL) was added to the mixture, and then the mixture was refluxed for15 min. Solvent was removed under reduced pressure to afford a white solid. Water (20 mL), 1,4-dioxane (15 mL), sodium hydroxide (1M solution in water, 20 mL), and di-tert-butyl dicarbonate (2.4 g, 11.9 mmol) at 0 C were added to the residue. The mixture was stirred at 0 C for 30 min and then warmed to room temperature and stirred overnight. After the reaction, a saturated aqueous ammonium chloride solution was added to the mixture. Compounds were extracted with chloroform, and the organic layer was dried with sodium sulfate. The solvent was removed under reduced pressure. Purification by silica gel flash-chromatography (hexane / ethyl acetate=1 / 1) yielded 1 (1.79 g,9.6 mmol, 97%) as a colorless oil. 1H NMR (300 MHz, CDCl3) delta; 4.42(broad s, 1H), 3.91-3.73 (m, 4H), 2.32 (broad s, 1H), 2.24-2.13 (m,1H), 1.96 (broad s, 1H), 1.45 (s, 9H). 13C NMR (75 MHz, CDCl3) delta;157.1, 80.1, 66.4, 63.5, 46.6, 28.2, 17.9. MS (FAB+) m/z; 188([M+H]+). HRMS (FAB+) m/z; 188.1282 (Calcd: 188.1287 forC9H18NO3+). [alpha]D20= -20.59 (c=1.19, CHCl3, determined on asample with 99.5% e.e.), lit.13 [alpha]D= -20.3 (c=0.72, CHCl3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.0% | With sodium bicarbonate; sulfuric acid; magnesium chloride; In tetrahydrofuran; water; ethyl acetate; toluene; | EXAMPLE 5 Synthesis of (S)-N-t-butoxycarbonylazetidine-2-methanol (Effect of Addition of t-butylmagnesium Chloride and Magnesium Chloride) STR12 In a nitrogen gas atmosphere, a reaction flask was charged with the isopropyl (2S)-4-oxo-2-azetidinecarboxylate obtained in Reference Example 2 (5.00 g, 31.8 mmol), magnesium chloride (4.54 g, 47.8 mmol) and THF (50 mL) and while maintaining the temperature of this solution at 5 to 15 C., t-butylmagnesium chloride (2 M solution in THF, 15.9 mL, 31.8 mmol) was added, followed by 1.5 hours of further stirring at that temperature. While maintaining the temperature of that solution at 5 to 15 C., a solution of lithium aluminum hydride (1.81 g, 47.8 mmol) in THF (10 mL) was added and, thereafter, the mixture was heated under reflux with stirring for 6 hours. The reaction mixture was then cooled to 5 C., water (100 mL) was added, and the mixture was further stirred at room temperature for 0.5 hour. This solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (3.37 g, 31.8 mmol) was then added, and di-t-butyl dicarbonate (7.63 g, 35.0 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 an oil (5.77 g). Based on its proton NMR spectrum (FIG. 5), said oil was identified as the desired product (S)-N-t-butoxycarbonylazetidine-2-methanol (yield 97.0%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.76 g | With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃; for 24h; | Borane tetrahydrofuran complex (1.0M solution in tetrahydrofuran,25.0 mL, 24.7 mmol) was added to a solution of L-azetidine-2-carboxtlicacid (5, 1.0 g, 9.9 mmol) in tetrahydrofuran (15.0 mL) under nitrogenatmospheric conditions. The resulting mixture was stirred for 90 minunder reflux. Afetr the reaction had cooled to room temperature, anaqueous solution of potassium hydrogen sulfate (10%, 15.0 mL) wasadded to the mixture, which was further refluxed for 15 min. Themixture was evaporated under reduced pressure to yield the residue of(S)-azetidine-2-ylmethanol. An aqueous solution of sodium hydroxide(1 M, 20.0 mL) and di-tert-butyl dicarbonate (2.4 g, 11.9 mmol) wereadded to a solution of (S)-azetidine-2-ylmethanol (862 mg, 9.9 mmol)in water (20.0 mL) and 1,4-dioxane (15.0 mL) at 0 C. The mixture wasthen stirred for 24 h at room temperature. The reaction mixture waspoured into a saturated aqueous solution of sodium bicarbonate andextracted with chloroform. The organic layer was dried over sodiumsulfate and concentrated under reduced pressure. The residue waspurified by silica gel column chromatography (n-hexane/ethylacetate=1/1) to yield (-)-6 (1.79 g, 97%) in the form of a colorless oil: 1H NMR (300 MHz, CDCl3) δ: 4.42 (br s, 1H), 3.91-3.73 (m, 4H),2.32 (br s, 1H), 2.24-2.13 (m, 1H), 1.96 (brs, 1H), 1.45 (s, 9H); 13CNMR (75 MHz, CDCl3) δ: 157.1, 80.1, 66.4, 63.5, 46.6, 28.2 (3), 17.87;IR (CHCl3) cm-1: 3400, 3005, 2978, 1666, 1414, 1369; FAB-MS m/z:188.1282 (Calcd for C9H18NO3: 188.1287); MS (FAB) m/z:188(M++H, 31); [α]D20=-20.59 (c=1.19, CHCl3). |
1.79 g | With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃;Inert atmosphere; | To a solution of L-azetidine-2-carboxylic acid (1.0 g, 9.9 mmol, >99% e.e.) in THF (15 mL), a borane-THF complex (1.0 M solution in THF, 25 mmoL) was added. The mixture was refluxed under a N2 stream for 1.5 hr. Potassium hydrogen sulfate (10% solution in water,15 mL) was added to the mixture, and then the mixture was refluxed for15 min. Solvent was removed under reduced pressure to afford a white solid. Water (20 mL), 1,4-dioxane (15 mL), sodium hydroxide (1M solution in water, 20 mL), and di-tert-butyl dicarbonate (2.4 g, 11.9 mmol) at 0 C were added to the residue. The mixture was stirred at 0 C for 30 min and then warmed to room temperature and stirred overnight. After the reaction, a saturated aqueous ammonium chloride solution was added to the mixture. Compounds were extracted with chloroform, and the organic layer was dried with sodium sulfate. The solvent was removed under reduced pressure. Purification by silica gel flash-chromatography (hexane / ethyl acetate=1 / 1) yielded 1 (1.79 g,9.6 mmol, 97%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ; 4.42(broad s, 1H), 3.91-3.73 (m, 4H), 2.32 (broad s, 1H), 2.24-2.13 (m,1H), 1.96 (broad s, 1H), 1.45 (s, 9H). 13C NMR (75 MHz, CDCl3) δ;157.1, 80.1, 66.4, 63.5, 46.6, 28.2, 17.9. MS (FAB+) m/z; 188([M+H]+). HRMS (FAB+) m/z; 188.1282 (Calcd: 188.1287 forC9H18NO3+). [α]D20= -20.59 (c=1.19, CHCl3, determined on asample with 99.5% e.e.), lit.13 [α]D= -20.3 (c=0.72, CHCl3). |