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Chemical Structure| 2591-86-8 Chemical Structure| 2591-86-8
Chemical Structure| 2591-86-8

N-Formylpiperidine

CAS No.: 2591-86-8

4.5 *For Research Use Only !

Cat. No.: A190252 Purity: 98%

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Product Details of [ 2591-86-8 ]

CAS No. :2591-86-8
Formula : C6H11NO
M.W : 113.16
SMILES Code : O=CN1CCCCC1
MDL No. :MFCD00006483
InChI Key :FEWLNYSYJNLUOO-UHFFFAOYSA-N
Pubchem ID :17429

Safety of [ 2591-86-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H311-H319
Precautionary Statements:P280-P305+P351+P338-P312
Class:6.1
UN#:2810
Packing Group:

Application In Synthesis [ 2591-86-8 ]

* 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 [ 2591-86-8 ]

[ 2591-86-8 ] Synthesis Path-Downstream   1~23

  • 1
  • [ 2591-86-8 ]
  • [ 109613-93-6 ]
  • 3,4-dimethoxy-2-formylpyridine [ No CAS ]
  • 3
  • [ 2591-86-8 ]
  • [ 116026-98-3 ]
  • [ 116026-99-4 ]
YieldReaction ConditionsOperation in experiment
65% Step 2: fert-Butyl 2-formylpyridin-3-ylcarbamate (10b)To a solution of compound 10a (2.9 g, 10.7 mmol) in THF (30 mL) was added n-BuLi (2.5M, 8.5 mL, 21.4 mmol) at -78C under N2 atmosphere and the resulting mixture was stirred for 1 h at this temperature. /V-Formylpiperidine (1.3 mL, 11.8 mmol) was added with rapid stirring. The mixture was stirred at 0C for 1 h and then partitioned with 1.5M HCI solution. The pH was adjusted to 7 by the addition of solid Na2C03. The aqueous layer was extracted with EA twice and the combined organic layers were dried over Na2S04, concentrated under reduced pressure and purified by CC (PE/EA = 3/1) to give compound 10b (1.5 g, 65%) as a white solid.
64.9% Add the compound (2-bromopyridin-3-yl) tert-butyl carbamate (20.1 g, 73.3 mmol), 200 mL of dry tetrahydrofuran to a 500 mL three-necked flask, and then N2 replacement protection after the temperature in the reaction flask drops to Slowly add n-BuLi (2.4 M, 73 mL) dropwise after -75C, keep the temperature in the reaction flask not to exceed -65C during the dropwise addition, continue to keep the temperature after the drop, and react for 1 h before adding 4-piperidinaldehyde (9.1 g, 80 mmol), stir for about 10 min after the addition, and then raise the temperature to 0C to react for 1 h. After the reaction was monitored by TLC, saturated ammonium chloride solution was added to quench the reaction, the reaction solution was extracted with ethyl acetate, the organic phases were combined, dried and purified by column chromatography (eluent: ethyl acetate-petroleum ether 1:9) to obtain the compound (2-Formylpyridin-3-yl) tert-butyl carbamate (10.6 g, 64.9%).
  • 4
  • [ 46346-67-2 ]
  • [ 110-89-4 ]
  • [ 2591-86-8 ]
  • [ 100-52-7 ]
  • [ 2905-56-8 ]
  • [ 100-51-6 ]
  • 5
  • [ 2591-86-8 ]
  • [ 58573-93-6 ]
  • [ 93972-08-8 ]
  • 6
  • [ 2591-86-8 ]
  • [ 867267-24-1 ]
  • [ 867267-25-2 ]
  • [ 867267-26-3 ]
  • 7
  • [ 2591-86-8 ]
  • [ 82257-14-5 ]
  • [ 82257-15-6 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; hexane; at -35℃; for 1.5h; A solution of (trimethylsilylmethyl) lithium (106 mL, 12.8 weight percent in hexanes) was charged to a 250 mL 3-neck round-bottom flask and cooled TO-40 C. A solution of 4-methoxypyridine (10.0 g) in tetrahydrofuran (THF) (111 mL) was added at less THAN-30 C over one hour. The lithiation was complete after about 1.5 hours. 1- FORMYLPIPERIDINE (10.6 g) was added at-35 C over 5 minutes. After 1.5 hours the reaction mixture was quenched with acetic acid (15 mL) and water (35 mL). The aqueous layer was separated and washed with 4x25 mL EtOAc. All organic layers were combined, dried over MGS04 and concentrated in vacuo to leave 16.0 g of yellow oil that crystallized on cooling. After trituration with 30 mL hexanes/1 mL isopropyl alcohol, this material was 96.5 % pure by GCarea% (13.02 g, 99% yield, corrected for assay). Recrystallization from IPA/hexanes (1: 3) gave an 83% yield of desired product as pale yellow crystals.
  • 8
  • [ 2591-86-8 ]
  • ammonium chloride [ No CAS ]
  • [ 119999-22-3 ]
  • [ 17610-20-7 ]
YieldReaction ConditionsOperation in experiment
3.5 g (85%) With n-butyllithium; In tetrahydrofuran; 22.2 mL (35.2 mmol) of n-butyl lithium (1.6 M in hexanes) was added. After 1 hours, a solution of 3.95 mL (35.5 mmol) of N-formylpiperidine was added to a solution of 5 g (17.8 mmol) of <strong>[119999-22-3]2-bromo-3-methyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene</strong> in 50 mL of tetrahydrofuran, cooled in a dry ice/acetone bath. After 30 minutes 30 mL of saturated aqueous ammonium chloride was added to the reaction mixture. The reaction mixture was warmed to room temperature and extracted with ethyl acetate. The organic phase was separated, washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel with gradient elution (hexane-10% ethyl acetate/hexane) to provide 3.5 g (85%) of 2-formyl-3-methyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene (m.p.: 82.4-84.1 C.).
  • 9
  • [ 2591-86-8 ]
  • [ 27139-97-5 ]
  • [ 58966-34-0 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; Step 1 5-chloro-2-methylbenzaldehyde To a solution of <strong>[27139-97-5]2-bromo-4-chlorotoluene</strong> (20.0 g; 97.3 mmol) in 300 mL of THF at -78° C. was added dropwise a 2.5 M solution of n-BuLi (102.2 mmol). After 30 min of stirring at that temperature, 1-formylpiperidine (11.4 mL) in 10 mL of THF was added and the solution left for 1 h. It was brought to 0° C., quenched with NH4OAc (25percent) and diluted with EtOAc. The organic phase was dried over Na2SO4, filtered and the solvent removed to yield 13.3 g of the title compound. 1H NMR (CDCl3) delta2.6 (3H, s), 7.15 (1H, d), 7.4 (1H, d), 7.75 (1H, s) and 10.2 (1H, s).
13.3 g (89%) With n-butyllithium; In tetrahydrofuran; Step 1 Ethyl (E)-3-(5-chloro-2-methylphenyl)-2-propenoate To 2-bromo-4-chloro toluene (20.0 g; 97.3 mmol) in 300 mL of THF at -78° C. was added n-BuLi 2.5M (40.8 mL) dropwise. After 20 min. 1-formylpiperidine (11.4 mL; 103.0 mmol) in 10 mL of THF was added dropwise. After 30 min the reaction mixture was brought to 0° C. and quenched with HCl (10percent) and diluted with EtOAc. The organic phase was collected, dry and the solvent evaporated to yield 13.3 g (89percent) of 5-chloro-2-methylbenzaldehyde.
  • 10
  • [ 2591-86-8 ]
  • [ 827343-55-5 ]
  • [ 20651-67-6 ]
  • [ 90965-06-3 ]
  • [ 827343-40-8 ]
  • [ 827343-37-3 ]
  • 11
  • [ 2591-86-8 ]
  • [ 54151-74-5 ]
  • [ 55218-76-3 ]
YieldReaction ConditionsOperation in experiment
1B. 4-Phenyl-pyridine-2-carbaldehyde: To a clear, colorless solution of lA (0.850 g, 4.5 mmol) in propionitrile (4.5 mmol) was added trimethylsilyl bromide (2.95 mL, 22.4 mmol). The resulting orange suspension was microwaved in a sealed tube at 150 C for 10 min. The reaction was cooled to rt and poured into 1.0 N NaOH containing ice. The aqueous layer was extracted with diethyl ether (2x). The combined organic layers were washed with sat. NaHC03, brine, dried over Na2S04, filtered and concentrated to give 1.07 g of 2-bromo-4-phenyl pyridine as an off-white solid. MS 233.9 (M+H) + and 235.9 (M+2+H)+. [00337] To a cooled (-78 C) clear, slightly yellow solution of 2-bromo-4- phenyl-pyridine (0.500 g, 2.14 mmol) in THF (8.6 mL) was added dropwise 2.5 M n-BuLi in hexane (0.86 mL, 2.14 mmol). The resulting red solution was stirred at-78 C for 1h, then 1-formylpiperidine (0.48 mL, 4.28 mmol) was added dropwise. The reaction was allowed to warm to 0 C over 1h and then stirred at 0 C for 1h. The reaction was quenched with 1.0 N HCl. The reaction was extracted with ethyl acetate. The combined organic layers were washed with sat. NaHC03, brine, dried over Na2S04, filtered, and concentrated to give 0.555 gas a golden oil. Column chromatography (40 g silica gel; gradient elution; 0-40% ethyl acetate/hexane) provided 1B (0.194 g, 49%) as a yellow solid. ¹H-NMR (400 MHz, CDCI3) No.: 10.16 (s, 1H), 8.84 (d, J = 5.3 Hz, 1H), 8.21 (d, J = 1.3 Hz, 1H), 7.75 (dd, J = 5.3, 1.8 Hz, 1H), 7.71-7.69 (m, 2H), 7.55-7.48 (m, 3H). MS 184.1 (M+H)+.
  • 12
  • [ 2591-86-8 ]
  • [ 161117-83-5 ]
  • 4-Formyl-2-methoxy-3-pyridinecarbamic acid 1,1-dimethylethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
A solution of 2- methoxypyridin-3-ylcarbamate (88; 100 mmol) in dry THF (350 mL) is cooled to - 78 0C, followed by drop wise addition of tert-butyllithium (120 mL, 2 M in pentane, 240 mmol) at a rate such that the temperature does not exceed -65 0C. The reaction is stirred at -78 0C for an additional 15 min., then at -20 0C for 1.5 h. Dry N- formylpiperidine (300 mmol) is added while maintaining the temperature below -15 0C, then the reaction is allowed to stir at room temperature overnight. The reaction is then cooled to 0 0C and quenched by addition of 1 N HCl to bring the pH to 2. Solid sodium carbonate is added to adjust the pH to 7. The solution is extracted with ethyl acetate and the combined organic layers washed with water and brine, dried with sodium sulfate, filtered and concentrated. The product 89 can be purified by silica gel column chromatography.
  • 13
  • [ 2591-86-8 ]
  • [ 138526-69-9 ]
  • [ 372519-10-3 ]
  • 14
  • [ 2591-86-8 ]
  • [ 1513-65-1 ]
  • [ 155601-65-3 ]
YieldReaction ConditionsOperation in experiment
60% Under N2, to a solution of 2,6-difluoropyridine (4.95 g, 43.0 mmol) in anhydrous THF (100 mL) cooled at- -78C was added LDA (2.0 M in heptane/THF/ethylbenzene, 23.0 mL, 46.0 mmol). After the mixture was stirred at -780C for 30 min 1-formylpiperidine (4.98 g, 44.0 mmol) was added. The mixture was stirred at -78C for 20 min, and at -78C aqueous HCl (3 N, 60 mL) and Et2O (50 mL) were added. The ether layer was collected and the aqueous layer was extracted with Et2O (3 X 100 mL). The combined extracts were dried over anhydrous Na2SO4. After filtration the solvent was removed, and the residue was purified by flash chromatography on silica gel (CH2Cl2/hexanes, 1:1 v/v) to afford 2,6-difluoro-pyridme-3- carbaldehyde as a pale yellow liquid (1.41 g, 60%).
  • 15
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  • [ 3769-42-4 ]
  • [ 25983-53-3 ]
  • 16
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  • [ 452-08-4 ]
  • [ 426831-32-5 ]
  • [ 1441770-51-9 ]
  • 17
  • [ 3240-35-5 ]
  • [ 2591-86-8 ]
  • 4-formyl-N-[(E)-piperidin-1-ylmethylidene]benzenesulfonamide [ No CAS ]
  • 18
  • [ 2591-86-8 ]
  • [ 100-44-7 ]
  • [ 2905-56-8 ]
YieldReaction ConditionsOperation in experiment
90% With NHC-Pd(II)-Im; sodium hydroxide; In water; at 50℃; for 3h;Inert atmosphere; Schlenk technique; General procedure: Under a N2 atmosphere, NaOH (3.0 equiv), NHC-Pd(II)-Im complex 1 (1.0 mol%), water (1.0 mL), benzyl chloride 2a (0.8 mmol), and N-formylmorpholine 3a (2.0 equiv) were successively added into a Schlenk reaction tube. The mixture was stirred at 50 C for 3 h. After cooling to room temperature, the reaction mixture was extracted with EtOAc, washed with brine, and dried over anhydrous Na2SO4. Then the solvent was removed under reduced pressure and the residue was purified by flash column chromatography on silica gel (eluent: PE/EA = 5:1) to give the pure products 4a. 1-Benzyl-piperidine (4o):15 Colourless liquid; 1H NMR (300 MHz): δ 7.31-7.21 (m, 5H), 3.47 (s, 2H), 2.35 (t, J = 4.8 Hz, 4H), 1.57 (pent,J = 5.4 Hz, 4H), 1.46-1.40 (m, 2H); 13C NMR (75 MHz): δ 138.6, 129.2, 128.1, 126.8, 63.9, 54.5, 25.9, 24.4.
81% With potassium hydroxide; In water; at 50℃; for 3h;Green chemistry; General procedure: KOH (2.4mmol), H2O (1.0mL), (pseudo)halides 1 (0.8mmol), and formamides 2 (1.6mmol) were successively added into a reaction tube. Then the reaction mixture was stirred under the conditions shown in Tables 1-5. After the reactions were completed, the mixture was extracted by ethyl acetate, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and purified by flash chromatography to give products 3.
  • 19
  • [ 2591-86-8 ]
  • [ 24591-33-1 ]
  • [ 31825-29-3 ]
  • 20
  • [ 2591-86-8 ]
  • [ 54396-44-0 ]
  • [ 868-85-9 ]
  • dimethyl (((2-methyl-3-(trifluoromethyl)phenyl)amino)(piperidin-1-yl)methyl)phosphonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With chitosan; In neat (no solvent); at 75℃; for 0.05h;Microwave irradiation; Green chemistry; General procedure: An equimolar mixture of <strong>[54396-44-0]2-methyl-3-(trifluoromethyl)aniline</strong> (0.351 g, 0.002 mol), corresponding aldehyde (0.002 mol), dimethyl phosphite (0.18 ml, 0.002 mol) and chitosan catalyst (10 molpercent) were taken in a reaction glass tube, degassed for 10 min and microwave irradiated at 180 W for 2 min at 60 °C. The progress of the reaction was monitored by TLC using petroleum ether and ethyl acetate (3:7) as solvent. After completion of the reaction, the mixture was diluted with ethyl acetate, washed with water (2 x 15 ml) followed by brine (1 x 10 ml), dried over Na2SO4 and evaporated to dryness. The crude mass was purified by column chromatography on silicagel (100-200 mesh) by using a 7:3 mixture of ethyl acetate in hexane to afford the pure alpha-aminophosphonates.
  • 21
  • [ 2591-86-8 ]
  • [ 150-78-7 ]
  • [ 7310-97-6 ]
YieldReaction ConditionsOperation in experiment
51% To a solution of 1-1 1 ,4-dimethoxybenzene (11.5 g, 83.26 mmol, 1 eq) in distilled Et20(276 mL) was added TMEDA (37,4 mL, 249.78 mmol, 3 eq). At 000, nBuLi at 2.5 M inhexane (100 mL, 249.78 mmol, 3 eq) was added dropwise. The mixture was stirred atreflux overnight under inert atmosphere. At 000, 1-formylpiperidine (27.74 mL, 249.78mmol, 3 eq). was added dropwise. The mixture was stirred at room temperature for 1 h.Following the addition of distilled water (300 mL) and HCI 3 M (57.5 mL), the mixture was extracted with hot CHCI3 (300 mLx4). The organic phase was dried over an hydrous Na2SO4 and filtered. After removing the solvent, the remaining residue was purified by recrystallization in CHCI3 to give an orange solid (9.51 g, 51 %).1H NMR (300 MHz, ODd3) 6 ppm = 10.51 (s, 2 H, CHO), 7.46 (s, 2 H, Ar), 3.95 (s, 6 H,OH3) data matched with literature reference
  • 22
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  • [ 636-98-6 ]
  • [ 6574-15-8 ]
  • 23
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  • [ 100-39-0 ]
  • [ 2905-56-8 ]
 

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