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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Synonyms: N-Methyl-4-piperidinol
4.5
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CAS No. : | 106-52-5 |
Formula : | C6H13NO |
M.W : | 115.17 |
SMILES Code : | OC1CCN(C)CC1 |
Synonyms : |
N-Methyl-4-piperidinol
|
MDL No. : | MFCD00006500 |
InChI Key : | BAUWRHPMUVYFOD-UHFFFAOYSA-N |
Pubchem ID : | 66048 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
With sodium chloride; In N-methyl-acetamide; ice-water; ethyl acetate; mineral oil; | EXAMPLE 11 5-Chloro-3-(1-methyl-4-piperidyloxy)-1,2-benzisoxazole A solution of 1.53 g (13.3 mmole) of 4-hydroxy-1-methylpiperidine in 25 ml of dimethylformamide was cooled to 5 C. in an atmosphere of nitrogen. 0.58 g (13.3 mmole) of sodium hydride (as a 55% w/w dispersion in mineral oil) was added to the solution, and then the solution was stirred at room temperature for 30 minutes. The reaction mixture was cooled to 5 C., and then 2.50 g (13.3 mmole) of <strong>[16263-53-9]3,5-dichloro-1,2-benzisoxazole</strong> were added to it; the resulting mixture was then stirred at 5 C. for 30 minutes and then at room temperature for 1 hour. At the end of this time, the mixture was poured into 50 ml of ice-water and then extracted twice, each time with 50 ml of ethyl acetate. The ethyl acetate layer was separated and washed with 100 ml of a 10% w/v aqueous solution of sodium chloride; it was then dried over anhydrous magnesium sulfate, and the drying agent was removed by filtration. The solvent was removed from the filtrate by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using ethyl acetate as the eluent to afford 2.38 g (yield 67.00%) of the title compound as a colorless powder, melting at 55-56 C. Infrared absorption spectrum (CHCl3) cm-1: 1535, 1470, 1440, 1360, 1310. Nuclear magnetic resonance spectrum (CDCl3) delta ppm: 1.73-3.00 (8H, multiplet); 2.32 (3H, singlet); 4.92 (1H, doubled doublet of doublets, J=13.5, 9.0 & 4.5 Hz); 7.30-7.76 (3H, multiplet). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In ethanol; hexane; N,N-dimethyl-formamide; | EXAMPLE 9 7-(1-Methyl-4--piperidyloxy)-1-cyclopropyl-6-fluoro-1,4-dihydro- 4-oxoquinoline-3-carboxylic acid (Compound No. 13) To a mixture of 530 mg of 6,7-difluoro-1-cyclopropyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 690 mg of N-methyl-4-piperidinol and 8 ml of DMF was added 320 mg of 60percent sodium hydride while the former was stirred under ice cooling. After the resultant mixture was stirred for 10 minutes at room temperature, 480 mg of acetic acid was added. DMF was distilled off under reduced pressure. To the residue was added 15 ml of n-hexane. The resultant mixture was thoroughly shaken and mixed. The supernatant was discarded. To the resultant precipitate was added 8 ml of ethanol, followed by stirring. A precipitate thus precipitated was collected by filtration, whereby 578 mg of the title compound was obtained. Melting point: 265°-269° C. 1 H-NMR (DMSO-d6) delta: 1.02-1.13(m,2H), 1.22-1.32(m,2H), 1.72-2.87(m,2H), 1.99-2.12(m,2H), 2.20(s,1H), 2.21-2.33(m,2H), 2.55-2.69(m2H), 3.68-3.80(m,1H), 4.70-4.81(m,1H), 7.68(d,1H,J=8Hz), 7.93(d,1H,J=12Hz), 8.62(s,1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; sodium carbonate; In diethyl ether; water; toluene; | REFERENCE EXAMPLE 1 1-Methyl-4-piperidyl 1,2-benzisoxazole-3-acetate hydrobromide p-Toluenesulfonyl chloride (2.16 g) and 4-hydroxy-1-methylpiperidine (4 g) were added in turn to a solution of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (2.0 g) in dry toluene (200 ml). The mixture was stirred overnight at room temperature and then shaken with 5% sodium carbonate (20 ml) and water (100 ml). The toluene layer was washed with water and dried over anhydrous sodium sulfate. The toluene was distilled off in vacuo and the residue was dissolved in diethyl ether. An ethanolic solution of 47% hydrobromic acid was added to the ether solution. The resulting crystals were collected by filtration and recrystallized from a mixture of ethanol and diethyl ether to give 1-methyl-4-piperidyl 2-(1,2-benzisoxazol-3-yl)acetate hydrobromide (2.8 g), m.p. 179-181 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With potassium tert-butylate; In tetrahydrofuran; at 20℃; for 1.16667h; | 14) l-[4-[(l-Methylpiperidin-4-yl)oxy]-3-(trifluoromethyl)phenyl]ethanamineA.4-[(l -Methylpiperidin-4-yl)oxy]-3-(trifluoromethyl)benzonitrile A mixture of 4-hydroxy-iV-methylpiperidine (133 mg, 1.15 mmol) and potassium tert-bu- toxide (150 mg, 1.27 mmol) in tetrahydrofuran (2.5 mL) was stirred under nitrogen for 10 min. <strong>[67515-59-7]4-Fluoro-3-(trifluoromethyl)benzonitrile</strong> (218 mg, 1.15 mmol) was added, and the 5 reaction mixture was stirred at ambient temperature for 1 h. The solvent was removed in vacuo, and the residue was partitioned between a 1 M NaOH solution and ethyl acetate. The organic layer was dried (Na2SO4) and evaporated. The residue was purified by column chromatography on silica gel (eluent: CHCl3/MeOH/conc. NH3, 95:5:0.5) affording 0.18 g (54% yield) of the pure product as a colourless solid. MS (APCI) m/z 285 [M+H]. 1H NMR o (400 MHz, DMSO-D6) delta ppm 1.67-1.74 (m, 2 H), 1.89-1.95 (m, 2 H), 2.16 (s, 3 H), 2.26- 2.31 (m, 2 H), 2.44-2.48 (m, 2 H), 4.78-4.82 (m, 1 H), 7.51 (d, J = 8.8 Hz, 1 H), 8.08 (dd, J = 8.8, 2.0 Hz, 1 H), 8.14 (d, J = 2.0 Hz, 1 H). |
Step 1 4-(1-methylpiperidin-4-yloxy)-3-trifluoromethylbenzonitrile 6.68 g of potassium t-butoxide was suspended in 40 ml of anhydrous tetrahydrofuran and a solution of 6.85 g of 1-methyl-4-hydroxypiperidine in 20 ml of anhydrous tetrahydrofuran was added dropwise over 35 minutes while stirring under ice-water cooling and further the mixture was stirred for 30 minutes. On the other hand, 7.50 g of <strong>[67515-59-7]4-fluoro-3-trifluoromethylbenzonitrile</strong> was dissolved in 40 ml of anhydrous tetrahydrofuran, the mixture was stirred under cooling in a dry ice/acetone bath, and the solution prepared earlier was added dropwise at the internal temperature of -70C. After adding dropwise, the reaction solution was stirred overnight while naturally heating up to room temperature. The reaction solution was ice-cooled, an aqueous saturated ammonium chloride solution and water were added thereto, and then the solvent was distilled off under reduced pressure. The residue was subjected to extraction with ethyl acetate twice. The extracts were washed in turn with water and saturated saline and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 7.31 g of the objective compound as colorless crystals. Melting point: 66-69C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7% | A solution of <strong>[3684-12-6]2-phenyl-2-(phenylamino)acetic acid</strong> (II) (234 mg, 0.91 mmol) in dioxane, is added with a 4M solution of HCl in dioxane (5 mL) and the reaction is stirred at RT for 1 h; the solvent is evaporated under reduced pressure to obtain a white solid which is dissolved in dry THF (10 mL). DCC (222 mg, 1.12 mmol), HOBt (144 mg, 1.14 mmol) and N-methyl-4-piperidinol (307 mg, 2.71 mmol) are added and the mixture is stirred for 96h at RT under nitrogen flowstream (LC-MS monitoring: complete conversion). The solvent is evaporated and the residue is partitioned between DCM and water; the organic layer is separated and dried over Na2SO4. The crude compound is purified by preparative LC-MS and the collected fractions are portioned between 2M K2CO3 and EtOAc. The 'organic phase is dried over Na2SO4, filtered and evaporated to dryness to obtain 20.6 mg of the title compound as a white solid (7% yield, racemic mixture).1H NMR (300 MHz, DMSO-d6) ppm: 7.45 - 7.60 (m, 2H), 7.20 - 7.45 (m, 3H), 6.95 - 7.17 (m, 2H), 6.69 (d, 2H), 6.47 - 6.63 (m, IH), 6.23 (d, IH), 5.20 (d, IH), 4.71 (tt, IH), 2.34 - 2.48 (m, IH), 2.11 - 2.25 (m, 2H), 2.09 (s, 3H), 1.94 - 2.08 (m, IH), 1.71 - 1.90 (m, IH), 1.51 - 1.71 (m, 2H), 1.29 - 1.51 (m, IH); LC-MS (ESI POS): 325.2 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 1h; | To a solution of 100 mg (0.766 mmol) of 4-hydroxy-1-methyl piperidine in 1.5 ml of tetrahydrofuran, 155 mg (1.53 mmol) of di-tert-butyl azocarboxylic acid, 402 mg (1.53 mmol) of triphenylphosphine and 0.170 ml (1.53 mmol) of <strong>[4983-28-2]2-chloro-5-hydroxypyrimidine</strong> were added, and the reaction solution was stirred at room temperature for 1 hour. After completion of the reaction, ethyl acetate was added to the reaction solution and the reaction solution was extracted with 1 N hydrochloric acid. 1 N sodium hydroxide aqueous solution was added to the aqueous layer to make its pH 10 and then the aqueous layer was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried with anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to provide 152 mg of the title compound as a white solid (yield: 87percent). 1H-NMR spectrum (400 MHz, CDCl3) delta ppm: 8.22 (2H, s), 4.33 (1H, tt, J=7.5, 3.8 Hz), 2.65-2.57 (2H, m), 2.30-2.22 (5H, m), 2.01-1.93 (2H, m), 1.85-1.75 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38.9% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0℃; | Take <strong>[66033-92-9]3-methyl-6-hydroxybenzo[d]isoxazole</strong> 2.0g, triphenylphosphine 4.2g,N-methyl-4-hydroxypiperidine 1.9g, tetrahydrofuran 40mL was added to the reaction flask and stirred.2.8 g of diethyl azodicarboxylate was dissolved in a small amount of tetrahydrofuran and added dropwise to the reaction flask.The system was browned to black, detected by TLC, and the reaction was completed, and the tetrahydrofuran was distilled off.Add water, extract with ethyl acetate, combine the organic phases, wash with brine,Dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to dryness to give a brown oil,Column chromatography gave 1.28 g of a white solid, yield 38.9%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | To a stirred solution of compound 78 (250 mg, 2.2 mmol, 1 eq) in DMF (5 mL) at 0 C was added NaH (60% in oil, 174 mg, 4.4 mmol, 2 eq) portion wise. After the mixture was stirred at room temperature for 30 mins, a solution of compound 77 (493 mg, 2.4 mmol, 1.1 eq) in DMF (2 mL) was added drop wise at 0 C. After the addition, the reaction was allowed to warm to room temperature and stirred overnight. After LC-MS indicated completion, water (21 mL) was added drop wise at 0 C and the mixture was extracted with EA (6 mL X 3). The combined organic layers was washed with brine (5 mL X 3) and dried over Na2S04, filtered and concentrated to afford the crude product, which was purified by silica gel column to give the desired product as a yellow solid (0.31 g, 50%). *H NMR (300 MHz, CDCb): delta 8.32 (s, 1 H), 7.56 (d, J= 1.5 Hz, 1 H), 7.45 (d, J= 8.1 Hz, 1 H ), 4.50 (s, 2 H), 3.47-3.45 (m, 1 H), 2.74- 2.72 (m, 2 H), 2.32 (s, 3 H), 2.28-2.25 (m, 2 H), 1.96-1.90 (m, 2 H), 1.79-1.72 (m, 2 H). LCMS: (M+H)+ = 285.0, 287.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.9% | With sodium hydride; In N,N-dimethyl-formamide; at 20℃; | To a solution of <strong>[19064-24-5]1,3-difluoro-2-nitrobenzene</strong> (1 g, 6.3 mmol) in DMF (20 mL) was added NaH (225 mg, 9.5 mmol) and 1-methylpiperidin-4-ol (870 mg, 7.55 mmol). The mixture was stirred at RT overnight and then the resulting mixture was quenched with water (30 mL), extracted with DCM (30 mL×3) and concentrated in vacuo to give a residue which was purified by silica gel column chromatography (DCM/MeOH=10/1) to give 4-(3-fluoro-2-nitrophenoxy)-1- methylpiperidine (1.0 g, 62.9%) as a green oil. LC-MS m/z: 255.2 [M+H]+. HPLC Purity (214 nm): 97%; tR = 0.40 min |
Tags: 1-Methylpiperidin-4-ol | Alcohols | Piperidines | Heterocyclic Building Blocks | Organic Building Blocks | 106-52-5
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H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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The concentration of the dissolution solution you need to prepare is mg/mL