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Chemical Structure| 191544-71-5 Chemical Structure| 191544-71-5
Chemical Structure| 191544-71-5
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Product Details of [ 191544-71-5 ]

CAS No. :191544-71-5
Formula : C13H21NO6
M.W : 287.31
SMILES Code : O=C(OC)C(C1)CC(C(O)=O)CN1C(OC(C)(C)C)=O
MDL No. :MFCD27979732

Safety of [ 191544-71-5 ]

Application In Synthesis of [ 191544-71-5 ]

* 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.

  • Downstream synthetic route of [ 191544-71-5 ]

[ 191544-71-5 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 4591-55-3 ]
  • [ 24424-99-5 ]
  • [ 191544-71-5 ]
  • [ 191544-71-5 ]
  • [ 595555-70-7 ]
YieldReaction ConditionsOperation in experiment
Reference Example 51 (3R*,5S*)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid, (3R*,5R*)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid and 1-tert-butyl 3,5-dimethyl piperidine-1,3,5-tricarboxylate [Show Image] Dimethyl pyridine-3,5-dicarboxylate (55 g) was dissolved in methanol (500 ml) and 6 M hydrochloric acid (70 ml), and rhodium-carbon (5.5 g) was added. The reaction mixture was stirred under pressurized hydrogen atmosphere (5 atm) at room temperature for 3 hr, and thereafter at 50C for 12 hr. The mixture was allowed to cool to room temperature, the rhodium catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethanol (300 ml) and, under ice-cooling, triethylamine (60 ml) and di-tert-butyl dicarbonate (68 g) were successively added. The reaction mixture was stirred at room temperature for 12 hr, and concentrated under reduced pressure. The residue was dissolved in 0.5 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography. The fraction eluted with hexane-ethyl acetate (7:1 - 1:4) was obtained. The less polar fraction was concentrated under reduced pressure to give 1-tert-butyl 3,5-dimethyl piperidine-1,3,5-tricarboxylate (22.2 g). The more polar fraction was concentrated under reduced pressure, and the residue was diluted with ethyl acetate. The precipitate was collected by filtration and washed with ethyl acetate to give (3R*,5S*)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid (15.6 g) as a powder. The filtrate was concentrated under reduced pressure to give a mixture (8.9 g) of (3R*,5S*)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid and (3R*,5R*)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid.(3R*,5S*)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid 1H-NMR (CDCl3) delta 1.47 (9H, s), 1.72 (1H, d), 2.41-2.63 (3H, m), 2.72 (2H, br s), 3.71 (3H, s), 4.38 (2H, d). Mixture of (3R*,5S*)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid and (3R*,5R*)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid 1H-NMR (CDCl3) delta 1.33-1.50 (9H, m), 1.60-1.82 (1H, m), 1.96-2.22 (1H, m), 2.41-2.58 (2H, m), 2.62-2.91 (2H, m), 3.34-3.91 (1H, m), 3.71 (3H, s), 4.37 (1H, br s), 7.55-8.47 (1H, m). 1-tert-butyl 3,5-dimethyl piperidine-1,3,5-tricarboxylate 1H-NMR (CDCl3) delta 1.36-1.50 (2H, m), 1.46 (7H, m), 1.62-1.76 (1H, m), 1.99-2.16 (1H, m), 2.38-2.55 (2H, m), 2.61-2.75 (1H, m), 2.81 (1H, t), 3.39-3.60 (1H, m), 3.64-3.81 (6H, m), 4.35 (1H, br s).
  • 2
  • [ 4591-55-3 ]
  • [ 24424-99-5 ]
  • [ 191544-71-5 ]
YieldReaction ConditionsOperation in experiment
Reference Example 34 (3R*,5S*)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid [Show Image] Dimethyl pyridine-3,5-dicarboxylate (55 g) was dissolved in methanol (500 ml) and 6 M hydrochloric acid (70 ml), and rhodium-carbon (5.5 g) was added. The reaction mixture was stirred under pressurized hydrogen atmosphere (5 atm) at room temperature for 3 hr and then at 50C for 12 hr. The mixture was allowed to cool to room temperature, the rhodium catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethanol (300 ml), and triethylamine (60 ml) and di-t-butyl dicarbonate (68 g) were successively added under ice-cooling. The reaction mixture was stirred at room temperature for 12 hr, and concentrated under reduced pressure. The residue was dissolved in 0.5 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography. The fraction eluted with hexane-ethyl acetate (7:1 - 1:4) was concentrated under reduced pressure. The residue was diluted with ethyl acetate, and the precipitate was collected by filtration and washed with ethyl acetate to give the object compound (15.6 g) as a powder. 1H-NMR (CDCl3) delta 1.47 (9H, s), 1.72 (1H, d), 2.41-2.63(3H, m), 2.72 (2H, br s), 3.71 (3H, s), 4.38 (2H, d).
  • 3
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  • 4
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  • cis-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid [ No CAS ]
  • [ 157226-76-1 ]
  • 1-tert-butyl 3,5-dimethyl piperidine-1,3,5-tricarboxylate [ No CAS ]
  • 5
  • [ 4591-55-3 ]
  • [ 191544-71-5 ]
  • 6
  • [ 4591-55-3 ]
  • [ 24424-99-5 ]
  • [ 191544-71-5 ]
  • [ 595555-70-7 ]
YieldReaction ConditionsOperation in experiment
To a solution of intermediate 2.147 (11.4 g, 58.3 mmol) in MeOH (58 mL) and 6 M aq. HCl (15 mL) was added rhodium on alumina (5%, 1.1 g). The resulting mixture was hydrogenated at 50 C while stirring under 200 bar pressure in a Parr reactor for 2 days. The reactor was then allowed to cool to room temperature and depressurized to ambient atmosphere. The crude heterogeneous resulting mixture was filtered through a bed of Celite and rinsed with MeOH. The filtrate was concentrated in vacuo, and the resulting product was carried forward without additional purification. (0663) [00227] To a precooled (0 C) solution of crude intermediate (11.7 g, 58.3 mmol assumed) in CH2Cl2 (60 mL) under N2 atmosphere was added triethylamine (33 mL, 230 mmol) then Boc anhydride (20 mL, 87 mmol). The resulting mixture was then allowed to warm to room temperature and stirred for 16 h, then quenched with H2O. The layers were separated, and the aqueous phase was extracted with CH2Cl2 (3x). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. Flash chromatography (SiO2, 75:25 hexanes:EtOAc, dry loaded Celite) afforded the product mixture as a clear colorless oil (3.08 g, 21% yield over 2 steps). The experimental data agreed with that in Imaeda, ACS Med. Chem. Lett.2016, 7 (10), 933-938.
 

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