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[ CAS No. 6574-15-8 ]

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CAS No. :6574-15-8 MDL No. :MFCD00023662
Formula : C11H14N2O2 Boiling Point : 363.5°C at 760 mmHg
Linear Structure Formula :- InChI Key :-
M.W :206.24 g/mol Pubchem ID :81049
Synonyms :

Safety of [ 6574-15-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

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  • Upstream synthesis route of [ 6574-15-8 ]
  • Downstream synthetic route of [ 6574-15-8 ]

[ 6574-15-8 ] Synthesis Path-Upstream   1~37

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  • [ 6574-15-8 ]
  • [ 2632-65-7 ]
YieldReaction ConditionsOperation in experiment
80% With palladium 10% on activated carbon; hydrazine hydrate In ethanol for 12 h; Reflux The second step: to install a magnetic stir, thermometer, condenser 500mL three-necked flask is addedThe first step in the reaction of 10.0g of 4-nitrophenyl pyrrolidine powder, 1.5g of 10percent mass fraction ofPd / C, was added 150mL ethanol as a solvent, to give a uniform suspension with stirring. After heating to reflux,The suspension was slowly added dropwise 32.0g mass fraction of 80percent hydrazine hydrate, stirring continued at reflux for 12h. ReactionIs completed, the reaction solution was filtered hot to remove Pd / C, the filtrate was concentrated under reduced pressure to 1/4 of its original volume, in a nitrogen atmosphereUnder cooling and crystallization, to give a gray crystalline 4-amino-phenyl pyrrolidine 6.8g, 80percent yield;;
Reference: [1] Patent: CN105503775, 2016, A, . Location in patent: Paragraph 0049
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  • [ 6574-15-8 ]
  • [ 2359-60-6 ]
YieldReaction ConditionsOperation in experiment
100% With palladium on activated charcoal; hydrogen In ethyl acetate at 20℃; for 3 h; 4-Fluoronitrobenzene (323 mg, 2.3 mmol) was dissolved in DMSO (5 ml), potassium carbonate (475 mg, 3.5 mmol) and piperidine (460 μl, 4.6 mmol) were added, and the mixture was stirred at 90° C. for 9 hr.
Then, water was added to the reaction solution, and the mixture was extracted twice with ethyl acetate.
The organic layer was washed twice with saturated aqueous NaCl.
The organic layer was dried over Na2CO3, the solvent was evaporated to give compound Y197 (yield; 472 mg, 100percent).
Compound Y197 was dissolved in ethyl acetate (20 ml), Pd/C (186 mg) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 3 hr.
Then, the reaction solution was filtered through celite, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (eluent; chloroform:methanol (40:1)) to give compound Y222 (yield, quantitative, 394 mg).
Compound Y491 (mentioned later) (80 mg, 0.18 mmol) was dissolved in dichloromethane (2 ml), compound Y222 (100 mg, 0.58 mmol) was added, and the mixture was stirred at room temperature for 5 hr.
Then, the solvent was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (eluent; chloroform:methanol (35:1)) to give the title compound (yield; 68 mg, 64percent).
1H NMR (500 MHz, CDCl3) δ8.40 (s, 1H), 8.0 (d, 1H, J=8.0 Hz), 7.70 (d, 1H, J=8.5 Hz), 7.52 (dd, 1H, J=8.0, 7.5 Hz), 6.92 (dd, 2H, J=9.0, 3.5 Hz), 6.77 (dd, 2H, J=9.0, 6.5 Hz), 5.33 (t, 1H, J=6.0 Hz), 4.07 (bs, 2H), 3.11-3.09 (m, 4H), 2.79-2.64 (m, 4H), 1.69-1.53 (m, 10H), 1.43 (s, 9H), 1.09-1.01 (m, 2H)
13C NMR (125 MHz, CDCl3) δ154.9, 141.6, 140.8, 131.4, 130.9, 129.8, 125.8, 125.7, 79.7, 77.4, 48.7, 36.6, 29.6, 28.6, 25.7, 24.2
HRMS (FAB-) m/z: [M-H]- calcd for C28H39N4O6S2, 591.2311. found, 591.2324
99% With palladium 10% on activated carbon; hydrogen In methanol at 20℃; A suspension of 1.01 g (5 mmol) 1-bromo-4-nitrobenzene, 1.5 g K2CO3, 0.59 mL (6 mmol) piperidine in 10 mL of DMF was heated to reflux overnight. Upon cooling, the reaction mixture was dilute with water, extracted with EA, and the organic layer was washed with water, followed by saturated NaCl aqueous solution, dried over anhydrous Na2SO4 and purified by flash chromatography (PE : EA = 50:1, 30:1) to afford 902 mg (87percent) yellow solid. The solid was dissolved in methanol, 90 mg Pd-C (10percent) was added and stirred under hydrogen overnight at room temperature and then filtered through Celite and concentratedin vacuo. The crude product was purified by flash chromatography (PEEA = 5:1) to afford 4l’ 0.706 g 99percent.
96%
Stage #1: With ammonium chloride In tetrahydrofuran; water at 75℃; for 0.5 h;
Stage #2: With water; iron In tetrahydrofuran at 75℃;
Synthesis of 4-Piperidin-1-yl-phenylamine
Ammonium chloride (228 mg, 4.2 mmol) in water (4 mL) was added to a solution of 1-(4-nitro-phenyl)-piperidine (220 mg, 1.0 mmol) in THF (6 mL) and the resulting mixture was stirred at 75° C. for 30 minutes.
Iron powder (238 mg, 4.2 mmol) was then added portion wise and the mixture stirred for 5 hours at 75° C.
The reaction mixture was filtered over celite, the filtrate was basified with sodium bicarbonate solution and the product extracted with ethyl acetate.
The organic layer was washed with brine solution, dried over Na2SO4 and concentrated to afford 180 mg (96percent) of 4-Piperidin-1-yl-phenylamine. LCMS: 177.13 (M+1)+, 80.6percent, 1H NMR: (DMSO-d6): δ 6.67 (m, 2H), 6.47 (m, 2H), 4.51 (s, 2H), 2.57 (t, 4H), 1.6 (q, 4H), 1.49 (m, 2H)
80% With palladium 10% on activated carbon; hydrazine hydrate In ethanol for 12 h; Reflux The second step: to install a magnetic stir, thermometer, condenser 500mL three-necked flask is addedThe first step in the reaction of 15.0g of 4-nitrophenyl piperidine powder, 2.0g of 10percent mass fraction of Pd / C,180mL of ethanol was added as a solvent, and stirred to obtain a uniform suspension. After heating to reflux, the suspensionWas slowly added dropwise 45.0g of mass fraction of 80percent hydrazine hydrate solution, stirring continued at reflux for 12h. The reaction was completeCompleted, the reaction solution was filtered hot to remove Pd / C, the filtrate was concentrated under reduced pressure to 1/4 of its original volume, under a nitrogen atmosphereCooling and crystallization, to obtain a gray 4-aminophenyl-piperidine 10.2 g of crystals, 80percent yield;
75% With palladium 10% on activated carbon; hydrazine hydrate In ethanol for 10 h; Reflux In a 500mL round-bottom flask, 28.3g (0.14mol) of nitro compound 1, 0.2g of 10 wtpercent Pd/C, 20mL hydrazine monohydrate and 180mL of ethanol was stirred at a reflux temperature for 10h. The solution was filtered hot to remove Pd/C, and the filtrate was evaporated under reduced pressure to dryness. A deep purplish red liquid was obtained. The product (2) was used for the next step without further purification. The yield was 18.1g (75percent). IR (KBr): 3429, 3346cm−1 (−NH2 str.). 1H NMR (500MHz, DMSO-d6, δ, ppm): 6.66 (d, J=8.8Hz, 2H, He), 6.48 (d, J=8.8Hz, 2H, Hd), 4.49 (s, 2H, −NH2), 2.84 (t, J=5.4Hz, 4H, Hc), 1.59 (m, 4H, Hb), 1.45 (m, 2H, Ha). 13C NMR (125MHz, DMSO-d6, δ, ppm): 143.5 (C4), 141.9 (C7), 118.6 (C6), 114.7 (C5), 52.1 (C3), 25.8 (C2), 23.8 (C1)
384 mg With iron; ammonium chloride In methanol; water at 100℃; General procedure: The compound S1 (261 mg, 1.25 mmol), iron powder (210 mg, 4.76 mmol, 3 equiv.) and ammonium chloride (335 mg, 6.27 mmol, 5 equiv.) were dissolved in methanol : water (2 : 1, 15 mL). The reaction mixture was heated at 100 °C overnight, cooled to RT, filtered through celite and the solvent was reduced under vacuum. The condensed mixture was extracted with DCM, washed with brine, dried with sodium sulfate and all solvent was evaporated to furnish the condensed residue, which was purified by flash chromatography (elution system - EA/Hexane = 1 : 1 ) to obtain the title compound (245 mg, 1.43 mmol).

Reference: [1] Patent: US2013/45977, 2013, A1, . Location in patent: Paragraph 0211; 0212; 0213; 0214
[2] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 15, p. 3057 - 3061
[3] Patent: US2009/239848, 2009, A1, . Location in patent: Page/Page column 25
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 12, p. 4849 - 4859
[5] Patent: CN105503775, 2016, A, . Location in patent: Paragraph 0042
[6] Reactive and Functional Polymers, 2016, vol. 108, p. 54 - 62
[7] Journal of Chemistry, 2014, vol. 2014,
[8] Journal of the American Chemical Society, 1948, vol. 70, p. 2223,2228
[9] Journal of Medicinal Chemistry, 2003, vol. 46, # 10, p. 1803 - 1806
[10] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 5, p. 1221 - 1227
[11] Journal of Medicinal Chemistry, 2005, vol. 48, # 7, p. 2371 - 2387
[12] Patent: WO2005/9978, 2005, A1, . Location in patent: Page 99; 101
[13] Patent: WO2005/42518, 2005, A2, . Location in patent: Page/Page column 99; 101
[14] Chemistry - A European Journal, 2011, vol. 17, # 9, p. 2763 - 2768
[15] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 5, p. 731 - 738
[16] European Journal of Medicinal Chemistry, 2018, vol. 158, p. 593 - 619
[17] European Journal of Medicinal Chemistry, 2019, p. 690 - 709
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  • [ 1207-69-8 ]
  • [ 6574-15-8 ]
  • [ 2359-60-6 ]
Reference: [1] Patent: US2001/46991, 2001, A1,
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  • [ 110-89-4 ]
  • [ 636-98-6 ]
  • [ 6574-15-8 ]
YieldReaction ConditionsOperation in experiment
95% With sodium acetate In N,N-dimethyl-formamide at 130℃; for 8 h; Aerobic conditions General procedure: A mixture of 1-iodo-4-nitro-benzene (1 mmol, 249 mg), pyrrolidine (2 mmol, 142 mg), Pd-MCM-48 (30 mg) and NaOAc (2 mmol, 164 mg) was heated at 130 °C in DMF (5 mL) for 12 h till completion of reaction (TLC). The reaction mixture was cooled to room temperature and catalyst was separated by filtration. The filtrate was extracted with ethyl acetate (20 mL), washed with water (5.x.1 mL), dried over Na2SO4. The solvent was evaporated to leave the crude product, which was purified by column chromatography over silica-gel (2percent ethyl acetate in hexane) to provide pure 1-(4-nitro-phenyl)-pyrrolidine (153 mg, 80percent). All the products listed in Table 3 are known in the literature and gave 1H and 13C NMR data consistent with the structures and data in the literature.
Reference: [1] Bulletin of the Chemical Society of Japan, 1991, vol. 64, # 1, p. 42 - 49
[2] Monatshefte fur Chemie, 2003, vol. 134, # 1, p. 37 - 43
[3] Organic and Biomolecular Chemistry, 2010, vol. 8, # 19, p. 4316 - 4321
[4] Tetrahedron, 2011, vol. 67, # 32, p. 5717 - 5724
[5] Organic Letters, 2013, vol. 15, # 8, p. 1918 - 1921
[6] Tetrahedron Letters, 1998, vol. 39, # 17, p. 2471 - 2474
[7] Journal of Chemical Research, 2013, vol. 37, # 2, p. 99 - 101
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  • [ 350-46-9 ]
  • [ 6574-15-8 ]
YieldReaction ConditionsOperation in experiment
100% With potassium carbonate In dimethyl sulfoxide at 90℃; for 9 h; 4-Fluoronitrobenzene (323 mg, 2.3 mmol) was dissolved in DMSO (5 ml), potassium carbonate (475 mg, 3.5 mmol) and piperidine (460 μl, 4.6 mmol) were added, and the mixture was stirred at 90° C. for 9 hr.
Then, water was added to the reaction solution, and the mixture was extracted twice with ethyl acetate.
The organic layer was washed twice with saturated aqueous NaCl.
The organic layer was dried over Na2CO3, the solvent was evaporated to give compound Y197 (yield; 472 mg, 100percent).
Compound Y197 was dissolved in ethyl acetate (20 ml), Pd/C (186 mg) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 3 hr.
Then, the reaction solution was filtered through celite, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (eluent; chloroform:methanol (40:1)) to give compound Y222 (yield, quantitative, 394 mg).
Compound Y491 (mentioned later) (80 mg, 0.18 mmol) was dissolved in dichloromethane (2 ml), compound Y222 (100 mg, 0.58 mmol) was added, and the mixture was stirred at room temperature for 5 hr.
Then, the solvent was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (eluent; chloroform:methanol (35:1)) to give the title compound (yield; 68 mg, 64percent).
1H NMR (500 MHz, CDCl3) δ8.40 (s, 1H), 8.0 (d, 1H, J=8.0 Hz), 7.70 (d, 1H, J=8.5 Hz), 7.52 (dd, 1H, J=8.0, 7.5 Hz), 6.92 (dd, 2H, J=9.0, 3.5 Hz), 6.77 (dd, 2H, J=9.0, 6.5 Hz), 5.33 (t, 1H, J=6.0 Hz), 4.07 (bs, 2H), 3.11-3.09 (m, 4H), 2.79-2.64 (m, 4H), 1.69-1.53 (m, 10H), 1.43 (s, 9H), 1.09-1.01 (m, 2H)
13C NMR (125 MHz, CDCl3) δ154.9, 141.6, 140.8, 131.4, 130.9, 129.8, 125.8, 125.7, 79.7, 77.4, 48.7, 36.6, 29.6, 28.6, 25.7, 24.2
HRMS (FAB-) m/z: [M-H]- calcd for C28H39N4O6S2, 591.2311. found, 591.2324
97% With potassium carbonate In dimethyl sulfoxide at 120℃; for 20 h; In a 250mL round-bottom flask equipped with a stirring bar, a mixture of 12.8g (0.15mol) of piperidine, 21.2g (0.15mol) of 4-fluoronitrobenzene, and 20.7g (0.15mol) of potassium carbonate (K2CO3) in 100mL of dimethyl sulfoxide (DMSO) was heated with stirring at 120°C for 20h. After cooling, the mixture was poured into 400mL mixed solution of ethanol/water (1:1). The yellow crystals were collected by filtration with a yield of 30.0g (97percent) and a melting point of 100–102°C, measured by differential scanning calorimetry (DSC) at a scan rate of 10°C/min. IR (KBr):1577, 1329cm−1 (−NO2 str.). 1H NMR (500MHz, DMSO-d6, δ, ppm): 8.02 (d, J=9.5Hz, 2H, He), 6.98 (d, J=9.5Hz, 2H, Hd), 3.49 (t, J=5.7Hz, 4H, Hc), 1.63 (m, 2H, Ha), 1.57 (m, 4H, Hb). 13C NMR (125MHz, DMSO-d6, δ, ppm): 154.5 (C4), 135.9 (C7), 125.8 (C6) 112.2 (C5), 47.5 (C3), 24.8 (C2), 23.8 (C1)
75% at 80℃; for 20 h; Synthesis of 1-(4-Nitro-phenyl)-piperidine
Piperidine (362 mg, 0.2 mmol) was added to a solution of 1-fluoro-4-nitro-benzene (200 mg, 1.4 mmol) in DMSO (10 mL) and the mixture was stirred at 80° C. for 20 hours.
The reaction mixture was diluted with water and extracted with ethyl acetate.
The organic layer was washed with brine solution, dried over Na2SO4 and concentrated to afford 220 mg (75percent) of 1-(4-nitro-phenyl)-piperidine.
54% With potassium hydroxide In dimethyl sulfoxide at 80℃; for 16 h; General procedure: A mixture of 2-fluorobenzamide (1a, 69.5 mg, 0.5 mmol), MeOH (ca. 32.0 mg, 1.0 mmol), KOH (56.0 mg, 1.0 mmol) and DMSO (2.0 mL) in a 25 mL screw-capped thick-walled Pyrex tube was stirred at room temperature for 16 h, and then water (10 mL) was added to the reaction mixture with stirring, and the mixture was extracted with ethyl acetate three times (3 * 10 mL). The combined organic phases were dried over Na2SO4 overnight. The filtered solution was concentrated under reduced pressure, and the crude residue was purified by column chromatography on silica gel with the use of petroleum ether/ethyl acetate/trimethylamine (gradient mixture ratio from 6:1:0.05 to 2:1:0.05 in volume) to afford 2aa as a white solid in 80percent yield (60.7 mg).
46% With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 5 h; Inert atmosphere Step Reaction: 15.0g equipped with a mechanical stirring was added a 500mL three-necked flask (176mmol)Piperidine, 24.9g (176mmol) of fluoro nitrobenzene, 24.5g (176mmol) of potassium carbonate was added 250mLOf N, N- dimethylformamide as the solvent, with stirring, under nitrogen, the reaction at 110 5H, coldAfter cooling, ice water discharge, the crude product was washed with water three times, dried, and recrystallized from ethanol to give yellowPiperidin-4-nitrophenyl powder 16.7g, 46percent yield;

Reference: [1] Journal of Organic Chemistry, 1981, vol. 46, # 18, p. 3634 - 3638
[2] Patent: US2013/45977, 2013, A1, . Location in patent: Paragraph 0211; 0212; 0213; 0214
[3] Reactive and Functional Polymers, 2016, vol. 108, p. 54 - 62
[4] Tetrahedron Letters, 1998, vol. 39, # 17, p. 2471 - 2474
[5] Synthetic Communications, 2008, vol. 38, # 4, p. 626 - 636
[6] Journal of the American Chemical Society, 2005, vol. 127, # 28, p. 9948 - 9949
[7] Monatshefte fur Chemie, 2003, vol. 134, # 1, p. 37 - 43
[8] Patent: US2009/239848, 2009, A1, . Location in patent: Page/Page column 24; 25
[9] Journal of Chemistry, 2014, vol. 2014,
[10] Tetrahedron, 2018, vol. 74, # 2, p. 303 - 307
[11] Patent: CN105503775, 2016, A, . Location in patent: Paragraph 0040; 0041
[12] Bulletin de la Societe Chimique de France, 1956, p. 311,315
[13] Organic Magnetic Resonance, 1982, vol. 18, # 2, p. 104 - 108
[14] Journal of Medicinal Chemistry, 2003, vol. 46, # 10, p. 1803 - 1806
[15] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 5, p. 1221 - 1227
[16] Journal of Medicinal Chemistry, 2005, vol. 48, # 7, p. 2371 - 2387
[17] Chemical Communications, 2005, # 22, p. 2857 - 2859
[18] Patent: US5580883, 1996, A,
[19] Patent: WO2005/9978, 2005, A1, . Location in patent: Page 99; 101
[20] Patent: WO2005/42518, 2005, A2, . Location in patent: Page/Page column 99
[21] Journal of Organic Chemistry, 2011, vol. 76, # 9, p. 3286 - 3295
[22] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 5, p. 731 - 738
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  • [ 6574-15-8 ]
Reference: [1] Synthesis, 1990, # 12, p. 1145 - 1147
[2] Synlett, 1999, # 10, p. 1559 - 1562
[3] Organic Letters, 2004, vol. 6, # 6, p. 985 - 987
[4] Journal of Organic Chemistry, 2000, vol. 65, # 4, p. 1158 - 1174
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YieldReaction ConditionsOperation in experiment
93% With potassium carbonate In neat (no solvent) at 120℃; for 24 h; General procedure: In a conical flask (10 mL) a mixture of aryl halide (1 mmol),amine (3 mmol), K2CO3 (2 mmol), and Pd-PFMN catalyst (0.06 g, 1.2 molpercent) was stirred for 24 h. Afterward, themixture was cooled down to room temperature and the catalystwas magnetically separated from the reaction mixtureand washed with diethyl ether (2 × 10 mL) followed bydeionized and oxygen-free water (2 × 10 mL). The reusedcatalyst was dried for the next run. The aqueous phase wasextracted with diethyl ether (2 × 10 mL) and the combinedorganic phases were dried over Na2SO4. The products werepurified by column chromatography (hexane/ethyl acetate)to obtain the desired purity.
86% With solid-supported nano and microparticles of Pd(0) In N,N-dimethyl-formamide at 80℃; for 6 h; General procedure: A mixture of 4-nitrochlorobenzene (100 mg, 0.63 mmol), piperidine (63.86 mg, 0.75 mmol) and SS-Pd (284.5 mg, 0.01 mmol of Pd) in DMF was placed in round bottom flask. The reaction mixture was then heated at 80oC under magnetic stirring for 6h. The completion of reaction was monitored by TLC. After cooling to room temperature, the mixture was diluted with water and extracted with ethyl acetate three times. The combined organic layer was concentrated to yield the crude product, which was purified by silica gel column chromatography (hexane:EtOAc :: 90:10) to yield 1-(4-nitrophenyl)piperidine 22 as a yellowish solid (112 mg, 86percent), mp 104-105 oC; 1H NMR (300 MHz, CDCl3-d1) δ 1H NMR (300 MHz, CDCl3-d1) δ 8.05-8.09( m, 2H), 6.76-6.79( m, 2H), 3.43 (m, 4H), 1.68 (m, 6H) ; 13C NMR (75 MHz, CDCl3-d1) δ 155.28, 137.70, 126.27 (2C), 112.20 (2C), 48.72 (2C), 25.66 (2C), 24.61; HRMS (ESI) data: m/z calcd for [M+ H]+ C11H15N2O2 207.2490, obsd. 207.2472.
85% at 30℃; for 0.25 h; Green chemistry General procedure: To a solution of amine (1.2 mmol) dissolved in 20percent DES,aryl halide (1 mmol) was added at room temperature andstirred for appropriate time. The progress of the reactionwas monitored by TLC. After completion of the reactioncold water was added to the reaction mixture. The precipitatedsolid was filtered off, and recrystallized using ethanol.
63% With water; sodium t-butanolate In toluene at 105℃; for 20 h; Schlenk technique General procedure: An oven-dried Schlenk tube was charged with the aryl halide (2 mmol) and amine (2.5 mmol), FeOA–Pd (0.05 g, 0.04 mmol, 1.5 molpercent), base (3 mmol), solvent (5 mL) and additive. The resulting mixture was stirred for the appropriate time and temperature. After reaction completion the reaction mixture was then cooled to room temperature and the catalyst separated using a magnet, taken up in Et2O (4 mL), and washed with brine (5 mL). The resulting solution was dried over anhydrous MgSO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel.
600 mg With potassium carbonate In N,N-dimethyl-formamide at 20 - 100℃; General procedure: 1-Chloro-4-nitrobenzene (500 mg, 3.17 mmol) and K2CO3 (526 mg, 3.8 mmol, 1.2 equiv.) were added together with DMF (10 mL) and stirred at RT. Morpholine (440 µL, 5.1 mmol, 1.6 equiv.) was added to the reaction mixture which was heated at 100 °C overnight. After cooling down to RT, the mixture was extracted with EA. The EA layer was washed with DI-water three times and the combined water layers were back-extracted with EA three times. The combined EA extracts were dried (Na2SO4) and all solvent was evaporated under vacuum. The residue was purified by flash chromatography (elution system – EA : Hexane = 1 : 1 ) to give the title compound as a yellow solid (294 mg, 1.41 mmol).

Reference: [1] Bulletin of the Chemical Society of Japan, 1991, vol. 64, # 1, p. 42 - 49
[2] Chemistry Letters, 1987, p. 1187 - 1190
[3] Monatshefte fur Chemie, 2003, vol. 134, # 1, p. 37 - 43
[4] European Journal of Organic Chemistry, 2010, # 19, p. 3621 - 3630
[5] Synthetic Communications, 2000, vol. 30, # 24, p. 4479 - 4488
[6] New Journal of Chemistry, 2018, vol. 42, # 2, p. 812 - 816
[7] Journal of Organic Chemistry USSR (English Translation), 1987, vol. 23, p. 2277 - 2281[8] Zhurnal Organicheskoi Khimii, 1987, vol. 23, # 12, p. 2580 - 2586
[9] Journal of the Iranian Chemical Society, 2015, vol. 12, # 11, p. 2057 - 2064
[10] Chinese Journal of Chemistry, 2014, vol. 32, # 8, p. 685 - 688
[11] Synthetic Communications, 2008, vol. 38, # 4, p. 626 - 636
[12] European Journal of Organic Chemistry, 2015, vol. 2015, # 18, p. 4018 - 4023
[13] Tetrahedron Letters, 2012, vol. 53, # 39, p. 5318 - 5322
[14] Catalysis Letters, 2017, vol. 147, # 6, p. 1371 - 1378
[15] Tetrahedron Letters, 2013, vol. 54, # 9, p. 1120 - 1124
[16] Journal of the American Chemical Society, 2005, vol. 127, # 28, p. 9948 - 9949
[17] Tetrahedron Letters, 2016, vol. 57, # 2, p. 219 - 222
[18] European Journal of Organic Chemistry, 2010, # 33, p. 6404 - 6408
[19] Journal of the Chemical Society, 1927, p. 1117
[20] Chemische Berichte, 1888, vol. 21, p. 2279
[21] Journal of Organic Chemistry USSR (English Translation), 1987, vol. 23, p. 2277 - 2281[22] Zhurnal Organicheskoi Khimii, 1987, vol. 23, # 12, p. 2580 - 2586
[23] Chemical Communications, 2005, # 22, p. 2857 - 2859
[24] European Journal of Medicinal Chemistry, 2018, vol. 158, p. 593 - 619
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  • [ 110-89-4 ]
  • [ 586-78-7 ]
  • [ 6574-15-8 ]
YieldReaction ConditionsOperation in experiment
87% With potassium carbonate In N,N-dimethyl-formamideReflux A suspension of 1.01 g (5 mmol) 1-bromo-4-nitrobenzene, 1.5 g K2CO3, 0.59 mL (6 mmol) piperidine in 10 mL of DMF was heated to reflux overnight. Upon cooling, the reaction mixture was dilute with water, extracted with EA, and the organic layer was washed with water, followed by saturated NaCl aqueous solution, dried over anhydrous Na2SO4 and purified by flash chromatography (PE : EA = 50:1, 30:1) to afford 902 mg (87percent) yellow solid. The solid was dissolved in methanol, 90 mg Pd-C (10percent) was added and stirred under hydrogen overnight at room temperature and then filtered through Celite and concentratedin vacuo. The crude product was purified by flash chromatography (PEEA = 5:1) to afford 4l’ 0.706 g 99percent.
80% With sodium acetate In N,N-dimethyl-formamide at 130℃; for 8 h; Aerobic conditions General procedure: A mixture of 1-iodo-4-nitro-benzene (1 mmol, 249 mg), pyrrolidine (2 mmol, 142 mg), Pd-MCM-48 (30 mg) and NaOAc (2 mmol, 164 mg) was heated at 130 °C in DMF (5 mL) for 12 h till completion of reaction (TLC). The reaction mixture was cooled to room temperature and catalyst was separated by filtration. The filtrate was extracted with ethyl acetate (20 mL), washed with water (5.x.1 mL), dried over Na2SO4. The solvent was evaporated to leave the crude product, which was purified by column chromatography over silica-gel (2percent ethyl acetate in hexane) to provide pure 1-(4-nitro-phenyl)-pyrrolidine (153 mg, 80percent). All the products listed in Table 3 are known in the literature and gave 1H and 13C NMR data consistent with the structures and data in the literature.
41% With water; sodium t-butanolate In toluene at 105℃; for 20 h; Schlenk technique General procedure: An oven-dried Schlenk tube was charged with the aryl halide (2 mmol) and amine (2.5 mmol), FeOA–Pd (0.05 g, 0.04 mmol, 1.5 molpercent), base (3 mmol), solvent (5 mL) and additive. The resulting mixture was stirred for the appropriate time and temperature. After reaction completion the reaction mixture was then cooled to room temperature and the catalyst separated using a magnet, taken up in Et2O (4 mL), and washed with brine (5 mL). The resulting solution was dried over anhydrous MgSO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel.
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