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Chemical Structure| 99275-47-5 Chemical Structure| 99275-47-5

Structure of N-Boc-5-methoxyindole
CAS No.: 99275-47-5

Chemical Structure| 99275-47-5

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Product Details of [ 99275-47-5 ]

CAS No. :99275-47-5
Formula : C14H17NO3
M.W : 247.29
SMILES Code : O=C(N1C=CC2=C1C=CC(OC)=C2)OC(C)(C)C
English Name :tert-Butyl 5-methoxy-1H-indole-1-carboxylate
MDL No. :MFCD08272248
InChI Key :LPSLGTZFBDZNEK-UHFFFAOYSA-N
Pubchem ID :11831752

Safety of [ 99275-47-5 ]

Application In Synthesis of [ 99275-47-5 ]

* 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 [ 99275-47-5 ]

[ 99275-47-5 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 99275-47-5 ]
  • [ 99275-48-6 ]
YieldReaction ConditionsOperation in experiment
With iodine; tert.-butyl lithium; pentane 1) THF, -78 deg C, 1 h, 2) -78 deg C, 1 h; Yield given. Multistep reaction;
Stage #1: 1-(tert-butyloxycarbonyl)-5-methoxyindole With tert.-butyl lithium In tetrahydrofuran at -78℃; Stage #2: With iodine In tetrahydrofuran at -78℃; Preparation of tert-butyl 2-iodo-1H-indole-1-carboxylate (1a) General procedure: A solution of tert-butyl 1H-indole-1-carboxylate (9.5 mmol) in dry THF (25 mL) was cooled to -78 °C, to which was added slowly and dropwise a solution of tert-BuLi (10 mmol) in THF (~5 mL) for a duration of 10 min. The mixture was then stirred at -78 °C for 1 h. To this was added a pre-cooled (-78 °C) solution of iodine (25 mmol) in THF (25 mL) dropwise. The mixture was stirred at -78 °C for 3h. After completion of the reaction (indicated by TLC) the mixture was allowed to reach room temp, treated with saturated Na2S2O3 solution (10 mL) and extracted with dichloromethane (2 x 10 mL). The organic layers were collected, combined, washed with cold water (2 x 10 mL), dried over anhydrous Na2SO4, filtered and concentrated. The residue obtained was purified by silica gel column chromatography using 20-25% EtOAc-hexane as eluent to give the title compound as colourless oil.
  • 2
  • [ 138344-11-3 ]
  • [ 99275-47-5 ]
YieldReaction ConditionsOperation in experiment
84% With toluene-4-sulfonic acid In ethanol for 13h; Ambient temperature;
With hydrogenchloride In tetrahydrofuran Ambient temperature; Yield given;
  • 3
  • [ 1006-94-6 ]
  • [ 24424-99-5 ]
  • [ 99275-47-5 ]
YieldReaction ConditionsOperation in experiment
100% With dmap In tetrahydrofuran at 20℃; for 16h;
99% With dmap; triethylamine In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran at 20℃; for 19h;
97% In acetonitrile at 20℃; 48.A Step A: To a solution of 5-methoxyindole (3.00 g, 20.4 mmol) in CH3CN (15 mL) was added di-tert-butyl-dicarbonate (4.90 g, 22.4 mmol) and a catalytic amount of DMAP. The solution was stirred at room temperature overnight. The reaction mixture was diluted with cold 1 N HCl (30 mL) and extracted with EtOAc (3×30 mL). The organic phase was dried (Na2CO3) and concentrated under reduced pressure. Purification by flash column chromatography (CH2Cl2) gave N-tert-butyl-carboxylate-5-methoxyindole (4.89 g, 97%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.01 (d, J=8.3 Hz, 1H), 7.56 (d, J=3.3 Hz, 1H), 7.02 (s, 1H), 6.922 (dd, J=9.0 Hz, 2.5 Hz, 1H), 6.49 (d, J=3.6 Hz, 1H), 3.85 (s, 3H), 1.66 (s, 9H).
94% With dmap In dichloromethane at 20℃; for 8h; Inert atmosphere;
87% With dmap In dichloromethane at 20℃; for 14h; Schlenk technique; Inert atmosphere;
83% With cesium fluoride In N,N-dimethyl-formamide at 25 - 30℃; for 6h;
78% With dmap In dichloromethane at 0 - 20℃; Inert atmosphere;
76% With dmap In tetrahydrofuran at 20℃;
57.6% With dmap In acetonitrile at 20℃;
With n-butyllithium 1.) THF, hexane, from -60 deg C to -15 deg C, 30 min, 2.) THF, hexane, from -60 deg C, to RT, 30 min; Yield given; Multistep reaction;
With dmap In dichloromethane at 20℃; for 0.75h;
With dmap In dichloromethane at 20℃; for 1h;
With dmap In acetonitrile at 20℃; for 64h; I.1 Step 1: 5-Methoxy-indole-1-carboxylic acid tert-butyl esterTo a solution of 5-methoxyindole (4.11 g, 27.9 mmol) in MeCN was added di-tert- butyl dicarbonate (7.13 ml, 30.7 mmol) followed by DMAP (0.102 g, 0.838 mmol): The reaction mixture was stirred at RT for 64 hours. The reaction mixture was partitioned between EtOAc (75 ml) and cold 1 M HCI (50 ml), extracted with EtOAc (2 x 50 ml) and the combined organics washed with brine (2 x 50 ml). The organic portion was dried (Na2C03), filtered and concentrated in vacuo to yield a white solid. The solid was triturated with iso-hexane (15 ml) to afford the title compound as a white solid; 1H NMR (400 MHz, CDCI3) δ 8.04 (1 H, br d), 7.59 (1 H, d), 7.05 (1 H, d), 6.95 (1 H, dd), 6.52 (1 H, d), 3.88 (3H, s), 1.69 (9H, s).
With triethylamine In tetrahydrofuran for 48h; Reflux;
With triethylamine In tetrahydrofuran Reflux; General procedure for the synthesis of 5-substituted-tert-butyl 1H-indole-1-carboxylates (6a-e). General procedure: Di-tert-butyl dicarbonate (8.73 g, 40 mmol) and triethylamine (3.3 mL, 23.7 mmol) were added to a solution of appropriate indoles 4a-e (20 mmol) in tetrahydrofuran (10 mL). The reaction mixture was heated under reflux for 24-48 h. After cooling the solvent was evaporated under reduced pressure and the residue (derivatives 6a and 6c) was purified by column chromatography using dichloromethane or dichloromethane/petroleum ether (9/1) as eluent or recrystallized with ethanol (derivatives 6b, 6d, 6e). For compounds 6a,c-e see supporting information. Derivatives 6b, 6c and 6e were also reported with a different method [33].
With triethylamine In tetrahydrofuran Reflux;
With dmap In dichloromethane at 20℃; for 12h; Inert atmosphere;
In tetrahydrofuran Reflux;
99% Stage #1: 5-methoxylindole With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide In dichloromethane at 20℃; Inert atmosphere; Stage #2: di-<i>tert</i>-butyl dicarbonate In dichloromethane at 20℃; Inert atmosphere;
16.7 g With dmap; triethylamine In dichloromethane at 20℃; 15 Example 15. Preparation of tert-butyl 5-methoxy-1H-indole-1-carboxylate A solution of (Boc)20 (15.0 g, 68.6 mmol) in dichloromethane (20 ml) was added to a mixture of 5-methoxy-1H-indole 10.0 g, 68 mmol), triethylamine (13.7 g, 136 mmol), DMAP (80 mg) in dichloromethane (100 ml) and the reaction stirred overnight at room temperature. It was quenched with saturated NaHCCb solution (60 ml) and the phases separated. The aqueous layer was extracted with dichloromethane (2 x 30 ml). The combined organic portion was washed with brine and dried over MgSC . The solvent was removed, and the residue eluted through a silica gel pad using CH2Cl2/hexanes (1 :1) as eluent. The solvent was removed, and the residue was dried under vacuum to give the product as a white crystalline solid. Yield = 16.7 g.
With dmap In dichloromethane at 20℃; Preparation of tert-butyl 1H-indole-1-carboxylate General procedure: To a solution of indole (8.5 mmol) in dichloromethane (20 mL) was added di-tert-butyl dicarbonate (9.2 mmol) and 4-dimethylaminopyridine (DMAP, catalytic amount) were added and the mixture was stirred at room temperature for 12h. After completion of the reaction (indicated by TLC) the mixture was diluted with brine solution (10 mL). The organic layer was collected, dried over anhydrous Na2SO4, filtered and concentrated. The residue obtained was purified by silica gel column chromatography using 20-25% EtOAc-hexane as eluent to give the title compound as a pale yellow oil (yield 96%).
With dmap In tetrahydrofuran at 20℃; for 12h;
With dmap In tetrahydrofuran at 20℃;
With dmap In dichloromethane at 0 - 20℃; Inert atmosphere;

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[2]Kirchberg, Sylvia; Froehlich, Roland; Studer, Armido [Angewandte Chemie - International Edition, 2009, vol. 48, # 23, p. 4235 - 4238].
[3]Current Patent Assignee: CURIA - US2006/52378, 2006, A1 Location in patent: Page/Page column 107.
[4]Zhou, Jiao-Long; Ye, Meng-Chun; Sun, Xiu-Li; Tang, Yong [Tetrahedron, 2009, vol. 65, # 34, p. 6877 - 6881].
[5]Natho, Philipp; Yang, Zeyu; Allen, Lewis A. T.; Rey, Juliette; White, Andrew J. P.; Parsons, Philip J. [Organic and Biomolecular Chemistry, 2021, vol. 19, # 18, p. 4048 - 4053].
[6]Inahashi, Nobuyuki; Matsumiya, Ayako; Sato, Tsuneo [Synlett, 2008, # 2, p. 294 - 296].
[7]Caramenti, Paola; Nandi, Raj Kumar; Waser, Jerome [Chemistry - A European Journal, 2018, vol. 24, # 40, p. 10049 - 10053].
[8]Liu, Qiang; Zhao, Qing Yong; Liu, Jie; Wu, Pan; Yi, Hong; Lei, Aiwen [Chemical Communications, 2012, vol. 48, # 26, p. 3239 - 3241].
[9]McManus, Joshua B.; Nicewicz, David A. [Journal of the American Chemical Society, 2017, vol. 139, # 8, p. 2880 - 2883].
[10]Milbank, Jared B. J.; Tercel, Moana; Atwell, Graham J.; Wilson, William R.; Hogg, Alison; Denny, William A. [Journal of Medicinal Chemistry, 1999, vol. 42, # 4, p. 649 - 658].
[11]Vazquez, Enrique; Davies, Ian W.; Payack, Joseph F. [Journal of Organic Chemistry, 2002, vol. 67, # 21, p. 7551 - 7552].
[12]Mizuta, Masahiro; Seio, Kohji; Miyata, Kenichi; Sekine, Mitsuo [Journal of Organic Chemistry, 2007, vol. 72, # 14, p. 5046 - 5055].
[13]Current Patent Assignee: ATKINSON Benjamin;BEATTIE David;CULSHAW Andrew James;DEVEREUX Nicholas James;MCKENNA Jeffrey;DALE James - WO2011/92293, 2011, A1 Location in patent: Page/Page column 85-86.
[14]Carbone, Anna; Pennati, Marzia; Parrino, Barbara; Lopergolo, Alessia; Barraja, Paola; Montalbano, Alessandra; Spanò, Virginia; Sbarra, Stefania; Doldi, Valentina; De Cesare, Michelandrea; Cirrincione, Girolamo; Diana, Patrizia; Zaffaroni, Nadia [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 7060 - 7072].
[15]Carbone; Pennati; Barraja; Montalbano; Parrino; Spanò; Lopergolo; Sbarra; Doldi; Zaffaroni; Cirrincione; Diana [Current Medicinal Chemistry, 2014, vol. 21, # 14, p. 1654 - 1666].
[16]Carbone, Anna; Parrino, Barbara; Vita, Gloria Di; Attanzio, Alessandro; Span, Virginia; Montalbano, Alessandra; Barraja, Paola; Tesoriere, Luisa; Livrea, Maria Antonia; Diana, Patrizia; Cirrincione, Girolamo [Marine Drugs, 2015, vol. 13, # 1, p. 460 - 492].
[17]Minakata, Satoshi; Miwa, Hayato; Yamamoto, Kenya; Hirayama, Arata; Okumura, Sota [Journal of the American Chemical Society, 2021, vol. 143, # 11, p. 4112 - 4118].
[18]Spanò, Virginia; Attanzio, Alessandro; Cascioferro, Stella; Carbone, Anna; Montalbano, Alessandra; Barraja, Paola; Tesoriere, Luisa; Cirrincione, Girolamo; Diana, Patrizia; Parrino, Barbara [Marine Drugs, 2016, vol. 14, # 12].
[19]Pandit, Soumen; Pandey, Vinay Kumar; Adhikari, Amit Singh; Kumar, Suresh; Maurya, Arvind Kumar; Kant, Ruchir; Majumdar, Nilanjana [Journal of Organic Chemistry, 2023, vol. 88, # 1, p. 97 - 105].
[20]Current Patent Assignee: KARE CHEMICAL TECHNOLOGIES - WO2022/232931, 2022, A1 Location in patent: Page/Page column 37-38.
[21]Rao, Gajjela Venkata Nageswara; Dandamudi, Srilaxmi; Tej, Mandava Bhuvan; Chinnamaneni, Satya Vani; Vasireddy, Purna Chandra Rao; Kapavarapu, Ravikumar; Rao, Mandava Venkata Basaveswara; Pal, Manojit [Tetrahedron Letters, 2023, vol. 126].
[22]Zhou, Wei; Chen, Peng; Xie, Xiao-Qing; Wu, Yanli; Ding, Haixin; Yang, Ruchun; Song, Xian-Rong; Luo, Mu-Jia; Xiao, Qiang [Journal of Organic Chemistry, 2025, vol. 90, # 2, p. 1085 - 1095].
[23]Zhang, Li-Hua; Xie, Yang; Xuan, Jun [Chemical Communications, 2025, vol. 61, # 47, p. 8528 - 8531].
[24]Zhang, Huan; Ma, Chenchen; Yin, Fengfeng; Jiang, Yu; Du, Jiaqi; Lu, Peifang; Wang, Jianhua; Liu, Jitian; Li, Xiaoxun [Chinese Journal of Chemistry, 2025, vol. 43, # 23, p. 3157 - 3164].
  • 4
  • [ 99275-47-5 ]
  • [ 143262-11-7 ]
YieldReaction ConditionsOperation in experiment
99% With hydrogen In isopropyl alcohol at 80℃; for 3h;
  • 5
  • [ 99275-47-5 ]
  • [ 290331-71-4 ]
YieldReaction ConditionsOperation in experiment
96% Stage #1: 1-(tert-butyloxycarbonyl)-5-methoxyindole With Triisopropyl borate; lithium diisopropyl amide In tetrahydrofuran at 0℃; for 2h; Stage #2: With phosphate buffer In tetrahydrofuran Further stages.;
94% Stage #1: 1-(tert-butyloxycarbonyl)-5-methoxyindole With Triisopropyl borate; lithium diisopropyl amide In tetrahydrofuran at 0℃; for 1h; Stage #2: With hydrogenchloride In tetrahydrofuran; water 48.B Step B: To an ice-cold solution of N-tert-butyl-carboxylate-5-methoxyindole (2.45 g, 9.90 mmol) and triisopropyl borate (2.83 g, 15.1 mmol) in THF (12.5 mL) was added 2.0 M LDA (6.3 mL in THF, 12.5 mL). The reaction mixture was stirred at 0° C. for 1 h, after which it was quenched with 2 N HCl (aq, 30 mL), and then extracted with CH2Cl2 (40 mL). The organic phase was dried (Na2SO4) and concentrated under reduced pressure. Recrystalization of the concentrate in 1:1 CH3CN/H2O (40 mL) yielded N-tert-butyl-carboxylate-5-methoxy-2-indoleboronic acid (2.70 g, 94%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.18 (s, 2H), 7.95 (d, J=8.9 Hz, 1H), 7.07 (d, J=2.5 Hz, 1H), 6.87 (dd, J=9.0 Hz, 2.6 Hz, 1H), 6.55 (s, 1H), 3.77 (s, 3H), 1.59 (s, 9H).
89% Stage #1: 1-(tert-butyloxycarbonyl)-5-methoxyindole With Triisopropyl borate; lithium diisopropyl amide In tetrahydrofuran at 0 - 5℃; for 0.5h; Stage #2: With hydrogenchloride In tetrahydrofuran Further stages.;
Multi-step reaction with 2 steps 1.1: lithium tetramethylpiperidie / tetrahydrofuran / 1.33 h / -78 °C 1.2: tetrahydrofuran / 0.5 h / -78 °C 2.1: aq. HCl / tetrahydrofuran / 20 °C
Stage #1: 1-(tert-butyloxycarbonyl)-5-methoxyindole With Triisopropyl borate; lithium diisopropyl amide In tetrahydrofuran at 0 - 5℃; Inert atmosphere; Stage #2: With hydrogenchloride In tetrahydrofuran; water

  • 6
  • [ 99275-47-5 ]
  • [ 6832-16-2 ]
  • [ 728004-46-4 ]
  • [ 728004-44-2 ]
YieldReaction ConditionsOperation in experiment
1: 60% 2: 30% With phenylhydrazine In dichloromethane
  • 7
  • [ 99275-47-5 ]
  • [ CAS Unavailable ]
  • [ 681449-65-0 ]
YieldReaction ConditionsOperation in experiment
65% Stage #1: 1-(tert-butyloxycarbonyl)-5-methoxyindole With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 1.5h; Stage #2: (-)-menthyl (S)-1-naphthalenesulfinate In tetrahydrofuran; hexane at -78℃; for 24h; Further stages.;
  • 8
  • [ 99275-47-5 ]
  • [ CAS Unavailable ]
  • [ 681449-64-9 ]
YieldReaction ConditionsOperation in experiment
35% Stage #1: 1-(tert-butyloxycarbonyl)-5-methoxyindole With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 1.5h; Stage #2: (-)-menthyl (S)-2-methoxy-1-naphthalenesulfinate In tetrahydrofuran; hexane at -78℃; for 24h; Further stages.;
  • 9
  • [ 99275-47-5 ]
  • [ 1006-94-6 ]
YieldReaction ConditionsOperation in experiment
98% In various solvent(s) at 150℃; for 0.25h; microwave irradiation;
98% With 1,1,1,3',3',3'-hexafluoro-propanol at 150℃; for 0.25h; Microwave irradiation; 2 EXAMPLE 2; Following the procedure set forth in Example 1 (A) above, indole derivatives were deprotected using TFE or HFIP in a microwave reactor at 150° C. as set forth in Table 1 below.
98% With 1,1,1,3',3',3'-hexafluoro-propanol at 150℃; for 0.25h; Microwave irradiation; 1.A; 2 Example 1; (A) A solution of the N-Boc protected amine (1 mmol) in TFE (2,2,2-trifluoroethanol) or HFIP (hexafluoroisopropanol) (5 mL) was placed in a sealed microwave vial. The reaction mixture was heated (100°C or 150°C) in a Biotage - Initiator Sixty microwave reactor with stirring until the disappearance of the starting material was observed. After cooling to room temperature, the mixture was evaporated to dryness under reduced pressure. The crude product was purified by flash-column chromatography. 1H NMR and 13C NMR were measured on Bruker Avance DPX-300 NMR or Bruker Avance-300 NMR spectrometers, operating at a proton (1H) frequency of 300.13 MHz and carbon (13C) frequency of 75.43 MHz.Example 2 Following the procedure set forth in Example 1(A) above, indole derivatives were deprotected using TFE or HFIP in a microwave reactor at 150°C as set forth in Table 1 below.
95% With 2,2,2-trifluoroethanol at 150℃; for 1h; Microwave irradiation; 1.A; 2 Example 1; (A) A solution of the N-Boc protected amine (1 mmol) in TFE (2,2,2-trifluoroethanol) or HFIP (hexafluoroisopropanol) (5 mL) was placed in a sealed microwave vial. The reaction mixture was heated (100°C or 150°C) in a Biotage - Initiator Sixty microwave reactor with stirring until the disappearance of the starting material was observed. After cooling to room temperature, the mixture was evaporated to dryness under reduced pressure. The crude product was purified by flash-column chromatography. 1H NMR and 13C NMR were measured on Bruker Avance DPX-300 NMR or Bruker Avance-300 NMR spectrometers, operating at a proton (1H) frequency of 300.13 MHz and carbon (13C) frequency of 75.43 MHz.Example 2 Following the procedure set forth in Example 1(A) above, indole derivatives were deprotected using TFE or HFIP in a microwave reactor at 150°C as set forth in Table 1 below.
95% In acetonitrile at 300℃;
82% With potassium carbonate In methanol; water for 3.5h; Heating;

  • 10
  • [ 99275-47-5 ]
  • [ 75-78-5 ]
  • [ 1009563-45-4 ]
YieldReaction ConditionsOperation in experiment
61% Stage #1: 1-(tert-butyloxycarbonyl)-5-methoxyindole; dimethylsilicon dichloride With lithium diisopropyl amide In tetrahydrofuran; hexane at 0℃; for 18h; Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; hexane; water at 0℃; for 0.5h; Further stages.;
  • 11
  • [ 99275-47-5 ]
  • [ 221642-75-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 1.) n-butyllithium, 2.) SO2 / 1.) hexane, THF, -78 deg C, 30 min, 2.) hexane, THF, from -78 deg C to RT, 30 min 2: N-chlorosuccinimide / CH2Cl2 / 0.33 h / 0 °C 3: N-methylimidazole / CH2Cl2 / 22 h 4: 88 percent / trifluoroacetic acid / 1.17 h 5: 73 percent / H2 / PtO2 / tetrahydrofuran / 2.5 h / 2585.74 Torr
  • 12
  • [ 2564-83-2 ]
  • [ 99275-47-5 ]
  • [ 98-80-6 ]
  • [ 1173780-34-1 ]
YieldReaction ConditionsOperation in experiment
99% With potassium fluoride; palladium diacetate In propionic acid at 20℃; for 1h;
  • 13
  • [ 110-62-3 ]
  • [ 192189-10-9 ]
  • [ 1239950-39-0 ]
  • [ 99275-47-5 ]
YieldReaction ConditionsOperation in experiment
1: 52% 2: 5% Stage #1: 3-iodo-5-methoxyindole-1-carboxylic acid tert-butyl ester With TurboGrignard In tetrahydrofuran at 0℃; for 0.2h; Stage #2: pentanal In tetrahydrofuran at 0℃; for 0.116667h;
  • 14
  • [ 100-52-7 ]
  • [ 192189-10-9 ]
  • [ 1239950-38-9 ]
  • [ 99275-47-5 ]
YieldReaction ConditionsOperation in experiment
1: 48% 2: 5% Stage #1: 3-iodo-5-methoxyindole-1-carboxylic acid tert-butyl ester With TurboGrignard In tetrahydrofuran at 0℃; for 0.2h; Stage #2: benzaldehyde In tetrahydrofuran at 0℃; for 0.116667h;
 

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