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Chemical Structure| 40114-49-6 Chemical Structure| 40114-49-6
Chemical Structure| 40114-49-6

1-Benzyl-3-piperidone

CAS No.: 40114-49-6

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Cat. No.: A721971 Purity: 96%

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Product Details of [ 40114-49-6 ]

CAS No. :40114-49-6
Formula : C12H15NO
M.W : 189.25
SMILES Code : O=C1CN(CC2=CC=CC=C2)CCC1
MDL No. :MFCD00023277

Safety of [ 40114-49-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 40114-49-6 ]

* 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 [ 40114-49-6 ]

[ 40114-49-6 ] Synthesis Path-Downstream   1~6

  • 3
  • [ 50606-58-1 ]
  • [ 40114-49-6 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; for 3h; EXAMPLE 1; Compound 1 1-Benzyl-3-(4-trifluoromethyl-phenoxy)-piperidine-3-carboxylic acid 1-Benzyl-3-piperidone HCl salt hydrate (33 g, 0.135 mol) was suspended in methylene chloride (200 mL), and triethylamine (21 mL, 0.15 mol) was added to the suspension; which was stirred for three hours. The resultant mixture was washed with H2O (200 mLX 2) and 300 mL of brine, then dried over magnesium sulfate, filtered, and the methylene chloride was removed to give 1-Benzyl-3-piperidone.
With ammonia; In methanol; The free base of the HCl salt of commercially available 1-benzyl-piperidin-3-one (2) was obtained after filtration over SCX-2 (MeOH followed by 1 N NH3/MeOH) and subsequent evaporation.
With potassium carbonate; In water; N-BENZYL-3-PIPERIDONE HYDROCHLORIDE was converted to the free base by addition to aqueous K2CO3 followed by extraction into ethyl acetate. To a solution of N-benzyl-3-piperidone (2.19 g, 11.57 mmol) in ethanol was added sodium borohydride (NaBH4) (0.438 g, 11.57 mmol) slowly over ten minutes. The solution was allowed to stir at room temperature overnight, and then concentrated in vacuo. The residue was dissolved in 1.0 N HCI and washed twice with diethylether, then the aqueous solution was basified with 3.0 N KOH to a pH of 12, and then extracted 3 times with dichloromethane. The organic extract was then dried over NA2SO4, and concentrated in vacuo. The crude was determined to be 100% pure (1.900 g, 86%) by IC/MS (EI) : m/z 192.3 (M + 1).
With sodium hydroxide; In dichloromethane; water; 1-Benzyl-3-piperidine hydrochloride hydrate (1.02 g, 5.40 mmol) was suspended in methylene chloride, washed with 1 M NaOH, dried through cotton, and concentrated to give 1.02 g of free base material. The free base was dissolved in THF (40 mL) and cooled to 0 C. Phenyl magnesium bromide (3.0 M in ether, 8.10 mmol, 2.70 mL) was added dropwise over 30 min, at which point the solution was warmed to rt and stirred for 3 h. The mixture was then concentrated and the residue dissolved in methylene chloride. The resultant solution was washed with 10% saturated NH4Cl, dried through cotton and concentrated. Silica gel chromatography eluding with hexanes/ethyl acetate (3:1) gave 0.975 g of the title compound as a pale yellow oil.
With sodium carbonate; In water; Step 1: 1- benzyl-3-piperidone (44)Commercially available l-benzyl-3-piperidone monohydrochloride monohydrated salt (43) was neutralized with saturated sodium carbonate solution, extracted with EtOAc, dried over sodium sulphate, concentrated in vacuum and stripped with dry THF. The liquid mass was used as such for the next step.
With sodium hydroxide; In water; ethyl acetate; A mixture of the monohydrochloride hydrate salt of l-benzyl-piperidin-3-one ( 3.24 g) and EtOAc (25 mL) was washed with 1 M NaOH (1 x 15 mL then 1 x 10 mL) and saturated NaCl solution (2 x 10 mL), then dried (MgSO4), filtered and solvent was evaporated to give 2.269 g of l-benzyl-piperidin-3-one as a pale orange-brown liquid.1H NMR (CDCl3) delta 1.91-2.00 (m, 2H), 2.35 - 2.40 (m, 2H), 2.62 - 2.68 (m, 2H), 3.01(s, 2H), 3.59 (s, 2H), 7.37 - 7.24 (m, 5H).

  • 4
  • [ 77801-91-3 ]
  • [ 40114-49-6 ]
  • [ 50606-58-1 ]
  • [ 106-93-4 ]
  • 1-benzyl-3-[1-methyl-1H-indol-4-yl]-3-piperidinol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; ammonium chloride; magnesium; In tetrahydrofuran; dichloromethane; ethyl acetate; STEP B 1-benzyl-3-[1-methyl-1H-indol-4-yl]-3-piperidinol hydrochloride A mixture of 12 g of magnesium in 155 ml of tetrahydrofuran was refluxed while a solution of 38 g of 1-methyl-4-chloro-1H-indole, 4.5 ml of 1,2-dibromoethane and 115 ml of tetrahydrofuran was slowly added thereto. After the addition of a few drops of methyl iodide, the mixture was refluxed for 6 hours and was then cooled to 45 C. to form a solution to which a solution of 1-benzyl-3-piperidone (prepared from 50 g of <strong>[50606-58-1]1-benzyl-3-piperidone hydrochloride</strong>) in 115 ml of tetrahydrofuran was added dropwise. The mixture was refluxed for 2 hours and then allowed to cool to room temperature. The mixture was stirred for 16 hours and was then cooled in an ice bath while 200 ml of an aqueous saturated ammonium chloride solution was added dropwise thereto. The mixture was filtered and the filter was rinsed with water and ethyl acetate. The decanted aqueous phase was extracted with ethyl acetate and the organic phase was washed with aqueous sodium chloride solution and was evaporated to dryness under reduced pressure. The residue was taken up in ether and the solution was extracted with 1 N hydrochloric acid. The aqueous phase was made alkaline and was extracted with ethyl acetate. The organic phase was evaporated to dryness under reduced pressure and the 73.4 g of residue were chromatographed over silica gel. Elution with a 9-1 cyclohexane-triethylamine mixture yielded a product which was taken up in methylene chloride. The solution was filtered and the filtrate was evaporated to dryness under reduced pressure to obtain 60.5 g of 1-benzyl-3-[1-methyl-1H-indol-4-yl]-3-piperidinol. The said base was dissolved in 300 ml of ethyl acetate and a solution of hydrogen chloride in ethyl acetate was added to the solution dropwise until the pH was 4. The mixture was iced for 16 hours and was vacuum filtered and the recovered product was washed with ethyl acetate and dried at 50 C. under reduced pressure to obtain 59.6 g of 1-benzyl-3-[1-methyl-1H-indol-4-yl]-3-piperidinol hydrochloride melting at 250 C. Analysis: C21 H25 N2 O: molecular weight=356.90. Calculated: %C 70.67; %H 7.06; %N 7.85; %Cl 9.93. Found: %C 70.4; %H 6.9; %N 7.9; %Cl 10.1.
  • 5
  • [ 40114-49-6 ]
  • [ 129488-10-4 ]
  • [ 916991-31-6 ]
YieldReaction ConditionsOperation in experiment
80% With sodium tris(acetoxy)borohydride; acetic acid; In 1,1-dichloroethane; at 20℃; for 43h; To a solution of 5-amino-indazole-l-carboxylic acid tert-butyl ester (2.333 g, 10.0 mmol) and l-benzyl-piperidin-3-one (1.900 g, 10.0 mmol) in DCE (35 mL) was added NaBH(OAc)3 (95percent; 2.970 g, 13.3 mmol) followed by AcOH (0.58 mL, 10.1 mmol) at room temperature and stirring continued for 43 h. The reaction was washed with 1 M NaOH (50 mL) then the organic phase dried (MgSO4), filtered, adsorbed onto silica and purified by MPLC using gradient of 0 - 10percent /-PrOH in DCM yielding 3.24 g (80percent) of 5-(l-benzyl-piperidin-3-ylamino)-indazole-l-carboxylic acid tert-butyl ester as a brown foam. LC-MS (ESI) m/z 407 [M+H]+.
  • 6
  • [ 40114-49-6 ]
  • [ 358-23-6 ]
  • [ 171364-83-3 ]
  • [ 19733-56-3 ]
YieldReaction ConditionsOperation in experiment
9.3 g Example 1 Compound 3 (36.0 g, 0.19 mol) was dissolved in 190 mL of methylene chloride under a nitrogen atmosphere,Diisopropylethylamine (27.0 g, 0.21 mol) was added and the temperature was lowered to -60 C. Trifluoromethanesulfonic anhydride (59.2 g,0.21 mol) was added and reacted at this temperature. After the reaction, water was added, the temperature was raised to room temperature, the mixture was extracted with ethyl acetate, and saturated sodium bicarbonateAfter washing and drying of the organic phase, the solvent was distilled off under reduced pressure to give 44.5 g of compound 3 as a light yellow solid.Example 2 A mixture of compound 3 (39.0 g, 0.12 p-nitrophenyl boronate mol) under nitrogen was added 130 mL of tetrahydrofuranAfter dissolution, (31.4 g, 0.13 mol), palladium tetrakistriphenylphosphine (6.9 g, 6.0 mmol), potassium carbonate(33.1 g, 0.13 mol) and heated to reflux temperature and reacted at this temperature for 8 hours, after which time the system was lowered to roomThe reaction solution was filtered through celite and the filtrate was evaporated under reduced pressure to a partial solvent, the crystals precipitated at low temperature, filtered to give a mixture of compounds 5,6The compound was 37.5 g as a light brown solid.Example 3 In an autoclave, 110 mL of methanol was added to a mixture of compounds 5 and 6 (19.0 g, 0.065 mol), 30 mL of acetic acid was added, 1.5 g of palladium hydroxide was added,After the introduction of hydrogen, after 12 at atmospheric pressure for 24 hours, after the reaction,The solid was filtered off and most of the methanol in the filtrate was evaporated under reduced pressure. 130 mL of 1 mL sodium hydroxide solution was added and the mixture was stirred for 20 minutes.The mixture was extracted twice with ethyl acetate (2 * 100 mL), the organic phase was washed once with saturated citric acid (100 mL) and the organic phase was washed with anhydrous sodium sulfateDrying, the organic phase pressure steaming to give a pale yellow solid 9.3g.
 

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