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CAS No. : | 18621-18-6 | MDL No. : | MFCD02683887 |
Formula : | C3H8ClNO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | UQUPQEUNHVVNKW-UHFFFAOYSA-N |
M.W : | 109.55 | Pubchem ID : | 2759290 |
Synonyms : |
Azetidin-3-ol hydrochloride
|
Chemical Name : | Azetidin-3-ol hydrochloride |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-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 |
---|---|---|
In dichloromethane; | Step 1. DEEA (3.57 mL, 20.50 mmol) was added to a stirred mixture of 3-hydroxyazetidine hydrochloride (1.00 g, 9.11 mmol) and <strong>[50712-69-1]2-bromomethyl-5-chlorobenzonitrile</strong> (2.10 g, 9.11 mmol) in CH2Cl2 (75 mL). After 16 h the reaction mixture was concentrated and the residue was partitioned between ether and 1N HCl. The aqueous layer was washed with ether, made neutral with NaHCO3, saturated with NaCl and extracted into CH2Cl2. The organic layer was dried (Na2SO4) and evaporated to give 5-chloro-2-[(3-hydroxyazetidin-1-yl)methyl]benzonitrile (1.67 g) as a gum: 1H NMR (CDCl3, 400 MHz) delta 3.03 (m, 2H), 3.68 (m, 2H), 4.49 (t, J=6.2 Hz, 1H), 7.46 (d, J=8.6 Hz, 1H), 7.53 (d,d, J=2.2, 6.2 Hz, 1H), 7.60 (d, J=2.0 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With caesium carbonate; In 1,2-dimethoxyethane; at 120℃; for 2h;Inert atmosphere; capped; | To a 150 mL pressure reaction bottle under 2 was added 4-chloro-5- iodopyrimidine (884 mg, 3.68 mmol), azetidin-3-ol, HC1 (1.29 g, 11.8 mmol), cesium carbonate (8.40 g, 25.8 mmol), and 1 ,2-dimethoxyethane (19 mL). The reaction mixture was stirred, flushed with argon for 5 min, securely capped and heated at 120C for 2h. The reaction mixture was filtered reaction through small Celite plug by gravity, washed with dichloromethane (125 mL) and the volatiles evaporated in vacuo to give 950 mg (93%) of the title compound as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine; In isopropyl alcohol; at 75.0℃; for 2.0h; | To a mixture of 4, 6-diiodo-2-methoxypyrimidine (1.25 g, 3.45 mmol) in i-PrCH (20 mL) was added azetidin-3-ol hydrochloride (374 mg, 3.45 mmol) and TEA (3 mL). The mixture washeated to 75 °C and stirred for 2 hrs. The solvent was removed under vacuum and the residue was dispersed in water (20 mL). The mixture was extracted with EtOAc (100 mL x 2) and the combined organic layers were washed with brine (50 mL), dried over Na2SO4 and concentrated to give the title compound (1.06 g, yield 100percent) as white solid.LCMS: (mobile phase: 5-95percent Acetonitrile in 2.5 mm), Rt 1.33 mm, MS Calcd: 307; MSFound: 308 [M+H].1H NMR (300 MHz, DMSO-d6): oe 6.51 (s, IH), 5.76 (br s, 1H), 457-4.49 (m, 1H), 4.20-4.15 (m, 2H), 3.76-3.68 (m, 5H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triethylamine; In isopropyl alcohol; at 85.0℃; for 2.0h; | A suspension of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> (1.0 g, 5.6 mmol), azetidin-3-ol hydrochloride (614 mg, 5.60 mmol) and TEA (1.70 g, 16.8 mmol) in i-PrOH (20 mL) was heated to 85 °C and stirred for 2 hrs. The solvent was removed under vacuum and the residue was partitioned with EtOAc (50 mL) and water (50 mL). The aqueous layer wasextracted with EtOAc (30 mL x 3) and the combined organic layers were washed with brine, dried over Na2SO4 and concentrated to give the title compound (1.17 g, yield 97percent) as a white solid.1H NMR (400 MHz, CDCI3): oe 5.86 (s, 1H), 4.84-4.79 (m, 1H), 4.34-4.30 (m, 2H), 3.98-3.95 (m, 2H), 3.92 (s, 3H), 3.13 (brs, 1H).LCMS: 5-95percent CH3CN in 2.5 mm; Rt = 1.27 mm, [M+H]= 216. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.58% | Ethyl 2,4,5-trifluorobenzoylacetate (20.0 g, 0.081 mol) was added to a 250 mL reaction flask.Triethylorthoformate (21.6 mL, 0.130 mol), acetic anhydride (32.5 mL, 0.344 mol), stirring,Heating was started and the temperature of the feed was raised to 130 C. for 4.0 hours.After the reaction was completed, the solvent was distilled off under reduced pressure to obtain an oily liquid.Add 70 mL of N-methylpyrrolidone to make the oily liquidThe solution was dissolved, <strong>[247069-27-8]3,5-difluoro-2,6-diaminopyridine</strong> (13.8 g, 0.095 mol) was added, and the feed solution was warmed to 50C.Stir and stir for 1.5h. After the addition of anhydrous lithium chloride (6.12 g, 0.146 mol), DBU (11.37 g, 0.075 mol) was added, and the reaction temperature was controlled at 35 C. for 2.0 h.3-Hydroxyazetidine hydrochloride (8.45 g, 0.077 mol) was added, DBU (26.82 g, 0.176 mol) was slowly added, and the temperature was 35 C. for 2.5 h.After the reaction is complete, transfer to a 500 mL reaction flask and add 25 mL of ethyl acetate.Slowly add 145 mL of 10% citric acid solution.After the addition was completed, the temperature was adjusted to 20C, and the crystals were crystallized for 4.0 hours. The crystals were collected, and the mixture was collected by suction filtration. The cake was collected and dried in an oven at 60C to obtain 38.35 g of the intermediate I. The yield was 93.58%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With caesium carbonate; In dimethyl sulfoxide; at 90℃; for 2h; | Step 1: 2,6-Dibromo-4-methoxypyridine (1.0 g, 3.75 mmol), azetidine-3-ol hydrochloride (493 mg, 4.50 mmol) and cesium carbonate (2.4) g, 7.50 mmol)It was added to dimethyl sulfoxide (15 mL), and the reaction system was stirred at 90 C for 2 hours. The reaction was quenched by the addition of water (15 mL).Wash with brine, dry over anhydrous sodium sulfate, filter, concentrate under reduced pressure,The residue was purified by flash column chromatography ( petroleum ether / ethyl acetate=3/1) to afford 1-(6-bromo-4-methoxypyridin-2-yl)-3-hydroxyazetidine (400 mg) , 41%) is a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 2.1, Weigh acetic anhydride,The mass ratio of tert-butylamine and acetic anhydride is 1: 1.5,The temperature was raised to 112 C with stirring, and the boron trifluoride ether solution was mixed with another weighed acetic anhydride to prepare a mixed solution.The content of boron trifluoride etherate solution in the mixed solution is 46.8%,To the stirred acetic anhydride, add the 1-tert-butyl-3-hydroxyacetate obtained in step 1 and the mixed solution in sequence,The mass ratio of tert-butylamine and 1-tert-butyl-3-hydroxyacetate is 3: 1,The mass ratio of tert-butylamine to the mixed solution is 1: 1,The dropping time is 2h, and the reaction is 12h after the dropping is completed.After the reaction is completed, it is cooled to a temperature of 50 C and concentrated to dryness under reduced pressure.Remove acetic acid and acetic anhydride;Step 2.2, add hydrochloric acid with a mass fraction of 6% to the concentrated residue, the mass ratio of tert-butylamine to hydrochloric acid is 1: 1, warm to 99 C, and stir for 5h; |
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