Alternatived Products of [ 103039-88-9 ]
Product Details of [ 103039-88-9 ]
CAS No. : | 103039-88-9 |
MDL No. : | MFCD11045405 |
Formula : |
C9H17NO2
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Boiling Point : |
- |
Linear Structure Formula : | - |
InChI Key : | - |
M.W : |
171.24
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Pubchem ID : | - |
Synonyms : |
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Safety of [ 103039-88-9 ]
Application In Synthesis of [ 103039-88-9 ]
* 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.
- Upstream synthesis route of [ 103039-88-9 ]
- Downstream synthetic route of [ 103039-88-9 ]
- 1
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[ 33216-52-3 ]
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[ 103039-88-9 ]
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[ 1221567-82-3 ]
Yield | Reaction Conditions | Operation in experiment |
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With triethylamine; In 1-methyl-pyrrolidin-2-one; at 220℃; for 1h;Microwave irradiation; |
To a solution of ethyl Lambda/-Boc-4-methylpiperidine-4-carboxylate (130 mg, 0.47 mmol) in CH2CI2 (8 ml.) was added trifluoroacetic acid (0.86 ml_, 1 1 mmol) and the reaction stirred at r.t. for 2 hr before evaporation and aziotrope with toluene (2 x 25 ml). The crude was dissolved in NMP (4.3 ml) and <strong>[33216-52-3]3,4,5-trichloropyridine</strong> (135 mg, 0.74 mmol) was added followed by triethylamine (0.42 ml_, 3.0 mmol) and the mixture was heated in a microwave reactor at 220 0C for 60 min. The mixture was poured into a saturated solution of sodium hydrogen carbonate (50 ml.) and extracted with EtOAc (2 x 100 ml_). The combined organic extracts were washed with water (2 x 50 ml_), brine (50 ml_), dried (MgSO4) and concentrated under reduced pressure to give a crude pale brown/orange oil (175 mg). The crude product was purified by flash column chromatography on silica gel (cyclohexane, EtOAc, 99:1-88:12, biotage 25+S) to furnish the title compound as a clear colourless oil (85 mg, 56%), LC-MS (ESI, 4 min) R, 3.36 min, m/z 317 (100%, [M+H]+); m/z (ESI) C14H18N2O2CI2 requires 316.0745, found [M+H]+ 316.0745. |
- 2
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[ 189442-87-3 ]
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[ 103039-88-9 ]
Yield | Reaction Conditions | Operation in experiment |
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With trifluoroacetic acid; In dichloromethane; at 20℃; for 2h; |
To a solution of ethyl Lambda/-Boc-4-methylpiperidine-4-carboxylate (130 mg, 0.47 mmol) in CH2CI2 (8 ml.) was added trifluoroacetic acid (0.86 ml_, 1 1 mmol) and the reaction stirred at r.t. for 2 hr before evaporation and aziotrope with toluene (2 x 25 ml). The crude was dissolved in NMP (4.3 ml) and 3,4,5-trichloropyridine (135 mg, 0.74 mmol) was added followed by triethylamine (0.42 ml_, 3.0 mmol) and the mixture was heated in a microwave reactor at 220 0C for 60 min. The mixture was poured into a saturated solution of sodium hydrogen carbonate (50 ml.) and extracted with EtOAc (2 x 100 ml_). The combined organic extracts were washed with water (2 x 50 ml_), brine (50 ml_), dried (MgSO4) and concentrated under reduced pressure to give a crude pale brown/orange oil (175 mg). The crude product was purified by flash column chromatography on silica gel (cyclohexane, EtOAc, 99:1-88:12, biotage 25+S) to furnish the title compound as a clear colourless oil (85 mg, 56%), LC-MS (ESI, 4 min) R, 3.36 min, m/z 317 (100%, [M+H]+); m/z (ESI) C14H18N2O2CI2 requires 316.0745, found [M+H]+ 316.0745. |
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With hydrogenchloride; In 1,4-dioxane; at 20℃; for 1h; |
A solution of hydrochloric acid (12N, 12.5 mL) in dioxane (25 mL) is added to 4-methyl piperidine-1,4-dicarboxylic acid-1-tert-butyl ester-4-ethyl ester (7.5 g, 0.028 mol) and stirred at room temperature for 1 hr. The reaction mixture is concentrated under reduced pressure and the residue is treated with aqueous solution of sodium bicarbonate to adjust the pH to 8 - 9. It is again concentrated under reduced pressure and the residue is treated with dichloromethane. After drying over sodium sulfate solvent is removed to get the crude residue which is purified by column chromatography (silica gel 230-400 mesh, methanol:dichloromethane:ammonium hydroxide 14:85:1) to get 4-methylpiperidine-4-carboxylic acid ethyl ester. Following compounds, VI to XIV, can be prepared by following a process similar to compound V. |
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Step (b)A solution of hydrochloric acid (12N, 12.5 mL) in dioxane (25 mL) is added to 4-methyl piperidine-1 ,4-dicarboxylic acid-1 -tert-butyl ester-4-ethyl ester (7.5 g, 0.028 mol) and stirred at room temperature for 1 hr. The reaction mixture is concentrated under reduced pressure and the residue is treated with aqueous solution of sodium bicarbonate to adjust the pH to 8 - 9. It is again concentrated under reduced pressure and the residue is treated with dichloromethane. After drying over sodium sulfate solvent is removed to get the crude residue which is purified by column chromatography (silica gel 230-400 mesh, methanol:dichloromethane:ammonium hydroxide 14:85:1 ) to get 4-methylpiperidine-4- carboxylic acid ethyl ester. |
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With hydrogenchloride; In 1,4-dioxane; at 20℃; for 2h; |
Compound 2 (4.87 mmol) was dissolved in HCl/dioxane (20 mL). The mixture was stirred at RT for 2 h. The solvent was removed to give the product |
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With hydrogenchloride; In diethyl ether; dichloromethane; at 20℃; |
Ethyl 4-methylpiperidine-4-carboxylate To Intermediate 87 (7.92 g, 29.2 mmol) dissolved in DCM (50 mL) was added 2M HCl in diethyl ether (31.0 mL). The mixture was stirred at r.t. overnight. The solvent was removed in vacuo to afford the title compound (6.16 g, 102%) as an orange/brown solid. deltaH (300 MHz, DMSO-d6) 8.70 (br s, 2H), 4.13 (t, J 7.1 Hz, 2H), 3.24-3.11 (m, 2H), 2.93-2.75 (m, 2H), 2.13-2.02 (m, 2H), 1.61 (ddd, J 14.5, 10.6, 4.1, 2H), 1.20 (t, J 7.1 Hz, 3H), 1.19 (s, 3H). |
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With trifluoroacetic acid; In dichloromethane; at 25℃; for 1.5h; |
Compound 20-b (1.60 g, 5.90 mmol, 1.00 eq) was dissolved in dichloromethane (15.00 mL), and trifluoroacetic acid (7 mL) was added to the above solution. The reaction solution was maintained at 25C and stirred for 1.5 hours. After the reaction was completed, the reaction solution was concentrated to give the product of compound 20-c (1.12 g, crude) as a yellow oil, which was used directly in the next step without purification. LCMS m/z = 171.8 [M+H]+. |
Reference:
[1]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 244 - 248
[2]Patent: WO2010/41054,2010,A1 .Location in patent: Page/Page column 75
[3]Patent: EP2511275,2012,A1 .Location in patent: Page/Page column 15
[4]Patent: WO2012/140020,2012,A1 .Location in patent: Page/Page column 32
[5]Patent: WO2013/96744,2013,A1 .Location in patent: Page/Page column 196
[6]Patent: US2015/152065,2015,A1 .Location in patent: Paragraph 0582
[7]Patent: EP3456711,2019,A1 .Location in patent: Paragraph 0185; 0187
- 3
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[ 103039-88-9 ]
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[ 297172-16-8 ]
Yield | Reaction Conditions | Operation in experiment |
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L1AIH4 (367.80 mg, 9.93 mmol) was suspended in dry THF (30 mL) at 0 . Compound 3 (4.96 mmol) in dry THF (10 mL) was added slowly. The reaction mixture was stirred at RT overnight. The reaction mixture was quenched with water (0.37 mL) and 10% NaOH (0.37 mL), then water (1.11 mL) was added. The mixture was stirred at RT for 30 min and filtered. The filtrate was concentrated to give the product. |
- 4
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[ 103039-88-9 ]
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[ 389889-80-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 2 steps
1.1: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C
1.2: 0.5 h / 20 °C
2.1: triethylamine / dichloromethane / 20 °C |
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- 5
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[ 103039-88-9 ]
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[ 1003845-06-4 ]
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[ 1515922-46-9 ]
Yield | Reaction Conditions | Operation in experiment |
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In 1,4-dioxane; at 65℃; for 1h;Microwave irradiation; |
(2-Chloropyrimidin-5-yl)boronic acid (321 mg, 2.03 mmol) and ethyl 4-methyl- piperidine-4-carboxylate (347 mg, 2.03 mmol) were stirred in 1,4-dioxane (6 mL) and the mixture was degassed with nitrogen for 5 minutes. The tube was sealed and heated under microwave irradiation for 30 minutes at 65C. Further <strong>[1003845-06-4](2-chloropyrimidin-5-yl)boronic acid</strong> (36 mg, 0.23 mmol) was added and the mixture was heated under microwave irradiation for 30 minutes at 65C. The mixture was concentrated to afford the title compound, which was used without further purification. Method C HPLC-MS: MH+ mlz 294, RT 1.09 minutes |
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With triethylamine; In ethanol; at 80℃; for 3h; |
[2-(4-Ethoxycarbonyl-4-methylpiperidin-1-yl)pyrimidin-5-yl]boronic acid To <strong>[1003845-06-4](2-chloropyrimidin-5-yl)boronic acid</strong> (4.00 g, 25.3 mmol) were added Intermediate 88 (4.09 g, 23.9 mmol) and ethanol (40 mL). Triethylamine (9.0 mL, 64 mmol) was added and the mixture was heated at 80 C. for 3 h before concentrating in vacuo. The mixture was partitioned between water (100 mL) and EtOAc (100 mL). The aqueous layer was separated and re-extracted with EtOAc (2*100 mL). The organic layers were combined and washed with brine (100 mL) before separating, drying (Na2SO4), filtering under reduced pressure and removing the solvent in vacuo. The resulting brown foam was purified by column chromatography on silica, using 100% DCM to 30% MeOH/DCM, to afford the title compound (4.00 g, 74% purity) as a brown oil. LCMS (pH 10): MH+ m/z 294, RT 0.65 minutes (74%). |
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In 1,4-dioxane; at 65℃; for 1h;Inert atmosphere; Sealed tube; Microwave irradiation; |
(2-Chloropyrimidin-5-yl)boronic acid (321 mg, 2.03 mmol) and ethyl 4-methylpiperidine-4-carboxylate (347 mg, 2.03 mmol) were stirred in 1,4-dioxane (6 mL) and the mixture was degassed with nitrogen for 5 minutes. The tube was sealed and heated under microwave irradiation for 30 minutes at 65 C. Further <strong>[1003845-06-4](2-chloropyrimidin-5-yl)boronic acid</strong> (36 mg, 0.23 mmol) was added and the mixture was heated under microwave irradiation for 30 minutes at 65 C. The mixture was concentrated to afford the title compound, which was used without further purification. Method C HPLC-MS: MH+ m/z 294, RT 1.09 minutes. |
- 6
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[ 160809-38-1 ]
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[ 103039-88-9 ]
- 7
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[ 203521-95-3 ]
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[ 103039-88-9 ]
Yield | Reaction Conditions | Operation in experiment |
19 g |
With hydrogen; palladium(II) hydroxide; In methanol; at 20℃; for 4h; |
[0400] 20% palladium hydroxide (50% water content, 4.00 g) was added to a solution of 1 -benzyl 4-ethyl 4-methylpiperidine-l,4-dicarboxylate (34. Og) in methanol (340 mL), and the resultant was stirred for 4 hours at room temperature in a hydrogen atmosphere. After the catalyst was filtered off, the filtrate was concentrated under reduced pressure, thereby obtaining the title compound (19.0 g). 1H NMR (400 MHz, CDC13) 6 1.19 (3H, s), 1.26 (3H, t, J = 7.1 Hz), 1.31-1.42 (2H, m), 2.08 (2H, d, J = 13.6 Hz), 2.62-2.74 (2H, m), 2.87-2.96 (2H, m), 4.16 (2H, q, J = 7.1 Hz). |
- 8
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[ 103039-88-9 ]
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[ 188815-30-7 ]
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ethyl 1-(3-formyl-5-(trifluoromethyl)phenyl)-4-methylpiperidine-4-carboxylate
[ No CAS ]
Yield | Reaction Conditions | Operation in experiment |
10% |
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 100℃; |
A flask was charged with ethyl 4-methylpiperidine-4-carboxylate (1.00 g, 5.85 mmol, 1.00 equiv), DMSO (10 mL), <strong>[188815-30-7]3-fluoro-5-(trifluoromethyl)benzaldehyde</strong> (1.35 g, 7.03 mmol, 1.20 equiv), and DIPEA (2.26 g, 17.6 mmol, 3.00 equiv). The resulting solution was stirred overnight at 100 C. and quenched with water (50 mL). The resulting solution was extracted with DCM (2*80 mL) and the organic layers were combined, washed with brine (2*50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 200 mg (10% yield) of ethyl 1-(3-formyl-5-(trifluoromethyl)phenyl)-4-methylpiperidine-4-carboxylate as a yellow oil. LCMS (ESI, m/z): 344 [M+H]+. |