* 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.
Reference：
[1] Russian Journal of Organic Chemistry, 2009, vol. 45, # 9, p. 1349 - 1352
[2] Russian Journal of Organic Chemistry, 2009, vol. 45, # 9, p. 1349 - 1352
[3] European Journal of Organic Chemistry, 2017, vol. 2017, # 22, p. 3234 - 3239
2
[ 88-72-2 ]
[ 41252-97-5 ]
[ 10388-22-4 ]
[ 41252-98-6 ]
Reference：
[1] Russian Journal of Organic Chemistry, 2009, vol. 45, # 9, p. 1349 - 1352
3
[ 41252-97-5 ]
[ 84-58-2 ]
[ 939-79-7 ]
Reference：
[1] Chinese Journal of Chemistry, 2013, vol. 31, # 4, p. 449 - 452
4
[ 41252-97-5 ]
[ 83863-33-6 ]
Yield
Reaction Conditions
Operation in experiment
95%
With ammonium acetate In ethanol for 12 h; Heating / reflux
To a solution of 4-iodo-l-methyl-2-nitro-benzene (25.0 g, 107 mmol) in 300 mL of ethanol was added sulfided platinum (3.00 g) and ammonium formate (20.3 g, EPO <DP n="304"/>321 mmol). The mixture was heated to reflux for 12 h and then cooled to 22 °C, filtered through Celite.(R). and concentrated in vacuo. The resulting residue was diluted with H2O (300 mL) and extracted with 3 x 200 mL CH2Cl2. The organic fractions were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo to give b (21.1 g, 95percent): MS m/z = 234 (M+H).
58%
Stage #1: With hydrogenchloride; tin(ll) chloride In ethanol at 0 - 20℃;
To a solution of step-b product (17 g, 0.06 mol) in ethanol (238 ml, 14 times), cone. HCI (85 ml, 5 times) was added drop wise at 0 - 50C. Then Tin chloride (51.05 g, 0.226 mol, 3.5 eq) was added portion wise at rt and the overall reaction mass was stirred for 3 hrs. Progress of the reaction was monitored by TLC (30percent ethyl acetate/hexane, Rr0.4). On completion of the reaction, ethanol was distilled off completely under reduced pressure. Residue obtained was basified to a pH~12 - 14 with NaOH solution and the compound extracted with ethyl acetate (2 * 50 ml). Combined extract was dried over sodium sulfate and concentrated under reduced pressure to yield the required product as a black colored solid (14 g, 94percent yield).
Reference：
[1] Patent: WO2006/41773, 2006, A2, . Location in patent: Page/Page column 302-303
[2] Patent: WO2010/127855, 2010, A1, . Location in patent: Page/Page column 121; 122
[3] Justus Liebigs Annalen der Chemie, 1871, vol. 158, p. 337
5
[ 624-31-7 ]
[ 99-99-0 ]
[ 5326-39-6 ]
[ 41252-97-5 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1988, p. 1281 - 1286
6
[ 624-31-7 ]
[ 99-99-0 ]
[ 1608-47-5 ]
[ 32704-08-8 ]
[ 32704-10-2 ]
[ 5326-39-6 ]
[ 41252-97-5 ]
Reference：
[1] Journal of Organic Chemistry USSR (English Translation), 1988, vol. 24, # 11, p. 2029 - 2035[2] Zhurnal Organicheskoi Khimii, 1988, vol. 24, # 11, p. 2251 - 2258
7
[ 119-32-4 ]
[ 41252-97-5 ]
Yield
Reaction Conditions
Operation in experiment
82%
Stage #1: With sulfuric acid; sodium chloride; sodium nitrite In water at -2 - 0℃; for 0.75 h; Stage #2: With sodium iodide In water
4-Iodo-2-nitrotoluene: To a suspension of 4-methyl-3-nitroaniline (4.30 g, 28.26 mmol) in water (40 mL) cooled in ice-water bath, 98percent sulfuric acid (1.89 mL) was added cautiously (Herm et al., 2002, which is incorporated herein by reference). Sodium chloride was added into the ice-water bath to lower the temperature to minus 2° C., and a solution of NaNO2 (2.15 g, 31.10 mmol) in water (10 mL) was added at a rate that the reaction temperature did not exceed 0° C. Upon completion of the addition, the mixture was stirred at minus 2° C. for 45 minutes. This solution of the diazo compound was then carefully added (in small portions) to a boiling solution of NaI (12.89 g, 86 mmol) (CAUTION: vigorous gas evolution). Upon completion of the addition, the reaction mixture was cooled down to room temperature and extracted with methylene chloride (50 mL) four times. The combined organic phase was washed with saturated NaHCO3 (40 mL) and water (40 mL), dried over Na2SO4, concentrated in vacuo. The residue was purified by silica gel chromatography to yield 4-iodo-2-nitrotoluene (6.07 g, 82percent). 1H NMR (400 MHz, CDCl3): δ 8.28 (d, 1 H, J=1.8 Hz, Ph-H), 7.81 (dd, 1 H, J=2.2 and 8.1 Hz, Ph-H), 7.09 (d, 1 H, J=8.1 Hz, Ph-H), 2.55 (s, 3 H, CH3).
58%
Stage #1: With hydrogenchloride; sodium nitrite In water at 0 - 5℃; Stage #2: With potassium iodide In water at 0 - 5℃; Reflux
To a step-a product (35 g, 0.23 mol), 6N HCI (194 ml) was added drop wise at rt. Cooled the contents to 0 - 50C and HCI gas was bubbled. A solution of sodium nitrite (29.2 g, 0.42 mol, 1.84 eq) in water (1 10 ml) was added drop wise at 0 - 5°C and stirred for 10 min. Then a solution of potassium iodide (65.9 g, 0.39 mol, 1.78 eq) in water (100 ml) was added drop wise at 0 - 50C. Heated the reaction contents to a reflux temperature and allowed to reflux for 12 hrs. Progress of the reaction was monitored by TLC (15percent ethyl acetate/hexane, Rf-0.6). On completion of the reaction, cooled the reaction contents to rt and the compound extracted with DCM (2 * 100 ml). Combined extract was washed with hypo solution, dried over sodium sulfate and concentrated under reduced pressure. The crude obtained was purified by column chromatography (silica gel, pure hexane) to yield the required product as pale yellow colored solid (38 g, 58percent yield).
Reference：
[1] Patent: US9200319, 2015, B2, . Location in patent: Page/Page column 57; 58
[2] Angewandte Chemie - International Edition, 2001, vol. 40, # 17, p. 3148 - 3151
[3] Chemistry - A European Journal, 2002, vol. 8, # 6, p. 1485 - 1499
[4] Patent: WO2010/127855, 2010, A1, . Location in patent: Page/Page column 121; 122
[5] Justus Liebigs Annalen der Chemie, 1871, vol. 158, p. 337
[6] Journal of the Chemical Society, 1926, p. 478
[7] Justus Liebigs Annalen der Chemie, 1871, vol. 158, p. 337
8
[ 60956-26-5 ]
[ 41252-97-5 ]
Reference：
[1] Journal of the American Chemical Society, 2002, vol. 124, # 50, p. 14844 - 14845
9
[ 5437-38-7 ]
[ 41252-97-5 ]
Yield
Reaction Conditions
Operation in experiment
43%
With copper(I) oxide; potassium phosphate; bismuth (III) nitrate pentahydrate; palladium(II) trifluoroacetate; oxygen; sodium iodide In dimethyl sulfoxide at 170℃; for 20 h; Schlenk technique
In a Schlenk reaction tube equipped with a magnetic stirrer, 6.7 mg of palladium trifluoroacetate, 28.6 mg of cuprous oxide, and phosphorus were added.Potassium 6.4mg,3-methyl-2-nitrobenzoic acid, 36.2 mg,Sodium Iodide 36mg, Lanthanum nitrate pentahydrate 194mg and 2mLDimethyl sulfoxide.The reaction was heated at 170°C for 20 hours in the presence of oxygen.After the reaction is completed, distilled water is added to quench the reaction.Ethyl acetate was extracted 3 times for 10 mL each time, and the combined organic phases were concentrated to give 4-iodo-1-methyl-2-nitrobenzene.22.6 mg, yield 43percent.
Reference：
[1] Patent: CN107513020, 2017, A, . Location in patent: Paragraph 0096-0097
10
[ 88-72-2 ]
[ 41252-97-5 ]
Reference：
[1] Tetrahedron Letters, 2000, vol. 41, # 47, p. 9101 - 9104
[2] Russian Journal of Organic Chemistry, 2007, vol. 43, # 9, p. 1291 - 1296
[3] Russian Chemical Bulletin, 1999, vol. 48, # 7, p. 1291 - 1294[4] Izvestiya Akademi Nauk, Seriya Khimicheskaya, 1999, # 7, p. 1303 - 1306
[5] Russian Chemical Bulletin, 1999, vol. 48, # 7, p. 1291 - 1294[6] Izvestiya Akademi Nauk, Seriya Khimicheskaya, 1999, # 7, p. 1303 - 1306
[7] Russian Journal of Organic Chemistry, 2007, vol. 43, # 9, p. 1278 - 1281
[8] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1973, p. 595 - 599
[9] Russian Journal of Organic Chemistry, 2008, vol. 44, # 6, p. 935 - 936
11
[ 88-72-2 ]
[ 41252-97-5 ]
[ 41252-98-6 ]
Reference：
[1] Russian Journal of Organic Chemistry, 2009, vol. 45, # 9, p. 1349 - 1352
[2] Russian Journal of Organic Chemistry, 2009, vol. 45, # 9, p. 1349 - 1352
[3] European Journal of Organic Chemistry, 2017, vol. 2017, # 22, p. 3234 - 3239
Reference：
[1] Russian Journal of Organic Chemistry, 2009, vol. 45, # 9, p. 1349 - 1352
14
[ 624-31-7 ]
[ 99-99-0 ]
[ 5326-39-6 ]
[ 41252-97-5 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1988, p. 1281 - 1286
15
[ 88-72-2 ]
[ 41252-97-5 ]
[ 10388-22-4 ]
[ 5411-52-9 ]
Reference：
[1] Russian Chemical Bulletin, 1999, vol. 48, # 7, p. 1291 - 1294[2] Izvestiya Akademi Nauk, Seriya Khimicheskaya, 1999, # 7, p. 1303 - 1306
[3] Russian Chemical Bulletin, 1999, vol. 48, # 7, p. 1291 - 1294[4] Izvestiya Akademi Nauk, Seriya Khimicheskaya, 1999, # 7, p. 1303 - 1306
16
[ 624-31-7 ]
[ 41252-97-5 ]
Reference：
[1] Chemische Berichte, 1897, vol. 30, p. 3001
17
[ 624-31-7 ]
[ 99-99-0 ]
[ 1608-47-5 ]
[ 32704-08-8 ]
[ 32704-10-2 ]
[ 5326-39-6 ]
[ 41252-97-5 ]
Reference：
[1] Journal of Organic Chemistry USSR (English Translation), 1988, vol. 24, # 11, p. 2029 - 2035[2] Zhurnal Organicheskoi Khimii, 1988, vol. 24, # 11, p. 2251 - 2258
18
[ 41252-97-5 ]
[ 4637-24-5 ]
[ 115666-47-2 ]
Yield
Reaction Conditions
Operation in experiment
61%
Stage #1: With pyrrolidine In N,N-dimethyl-formamide at 110℃; for 4 h; Stage #2: With hydrogenchloride; titanium(III) chloride In water; N,N-dimethyl-formamide at 0℃; for 3 h;
6-Iodoindole (4): Starting material 3 (5.00 g, 19.0 mmol, 1.0 equiv) was dissolved in DMF (50 mL). DMFDMA (3.05 mL, 22.8 mmol, 1.2 equiv) was added, followed by pyrrolidine (1.90 mL, 23.1 mmol, 1.2 equiv). The mixture was heated to 110 °C for 4 h until complete consumption of starting material as monitored by TLC, and allowed to cool to rt. DMF (100 mL) and 4 M aqueous NH4OAc buffer (83 mL, 17.5 equiv) were added and the solution was cooled with an ice bath. An aqueous solution of 20percent TiCl3 in 3percent HCl (73.3 mL, 114.06 mmol, 6.0 equiv) was added via a dropping funnel. The reaction mixture was stirred for 3 h followed by extraction with TBME (3 × 100 mL). The organic phase was washed with 2 M NaOH (100 mL), H2O (100 mL) and dried with MgSO4. After evaporation of the solvent the raw material was prepurified by short column chromatography [PE/EA (15:1)] to be sublimated in HV at 110–115 °C to give the product as a slightly yellowish solid (2.83 g, 11.6 mmol, 61percent). TLC [PE/EA (10:1)]: Rf = 0.25. Mp.: 103-105 °C. 1H NMR (400 MHz, CDCl3): = 8.10 (sbr, 1H, NH), 7.75 (dd, 1H, J = 2.0 Hz, J = 1.0 Hz, 4-H), 7.40-7.39 (m, 2H, 5-H and 7-H), 7.13 (dd, 1H, J = 3.2 Hz, J = 2.5 Hz, 2-H), 6.52 (ddd, 1H, J = 3.1 Hz, J = 2.0 Hz, J = 0.9 Hz, 3-H). 13C NMR (100 MHz, CDCl3): = 137.1 (1C, C-7a), 128.7 (1C, C-7), 127.2 (1C, C-3a), 124.5 (1C, C-2), 122.4 (1C, C-5), 120.0 (1C, C-4), 102.9 (1C, C-3), 85.8 (1C, C-6). IR (ATR): = 3888 (w), 3410 (s), 3094 (w), 3073 (w), 2925 (w), 1884 (w), 1726 (w), 1624 (w), 1597 (w), 1563 (w), 1493 (w), 1449 (m), 1392 (m), 1331 (m), 1309 (m), 1270 (w), 1232 (w), 1199 (w), 1090 (m), 1059 (w), 1043 (w), 998 (m), 944 (w), 878 (m), 858 (m), 802 (s), 759 (m), 727 (s), 651 (w), 607 (m), 586 (m), 565 (w). UV-Vis (MeOH): max (lg ) = 202 (4.32), 227 (4.62), 279 (3.86), 285 (3.86). MS (EI, 70 eV): m/z (percent) = 243 [M]+ (100), 116 [M–I]+ (56), 89 (26), 63 (12)
Reference：
[1] Organic Letters, 2017, vol. 19, # 23, p. 6296 - 6299
[2] Beilstein Journal of Organic Chemistry, 2015, vol. 11, p. 1700 - 1706
With ammonium acetate;platinum, sulfided; In ethanol; for 12h;Heating / reflux;
To a solution of 4-iodo-l-methyl-2-nitro-benzene (25.0 g, 107 mmol) in 300 mL of ethanol was added sulfided platinum (3.00 g) and ammonium formate (20.3 g, EPO <DP n="304"/>321 mmol). The mixture was heated to reflux for 12 h and then cooled to 22 C, filtered through Celite and concentrated in vacuo. The resulting residue was diluted with H2O (300 mL) and extracted with 3 x 200 mL CH2Cl2. The organic fractions were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo to give b (21.1 g, 95%): MS m/z = 234 (M+H).
58%
To a solution of step-b product (17 g, 0.06 mol) in ethanol (238 ml, 14 times), cone. HCI (85 ml, 5 times) was added drop wise at 0 - 50C. Then Tin chloride (51.05 g, 0.226 mol, 3.5 eq) was added portion wise at rt and the overall reaction mass was stirred for 3 hrs. Progress of the reaction was monitored by TLC (30% ethyl acetate/hexane, Rr0.4). On completion of the reaction, ethanol was distilled off completely under reduced pressure. Residue obtained was basified to a pH~12 - 14 with NaOH solution and the compound extracted with ethyl acetate (2 * 50 ml). Combined extract was dried over sodium sulfate and concentrated under reduced pressure to yield the required product as a black colored solid (14 g, 94% yield).
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; bis(pinacol)diborane; In dichloromethane; dimethyl sulfoxide; at 85℃; for 3h;Schlenk technique; Inert atmosphere;
To a oven-dried Schlenk tube was added <strong>[41252-97-5]4-iodo-2-nitrotoluene</strong> (1.97 g, 7.5 mmol), catalyst PdCl2(dppf).CH2Cl2 (0.31 g, 0.38 mmol), anhydrous potassium carbonate (3.11 g, 22.5 mmol) and bis(pinacolato)diboron (0.95 g, 3.75 mmol). Anhydrous DMSO (40 mL) was added into the mixture, and the resulted solution was stirred at 85 C. for 3 h under argon. The reaction solution was cooled to room temperature, and added H2O and EtOAc. The combined organic phase was washed with H2O and brine, respectively. After evaporation, the crude product was purified by flash chromatography (elute hexane/EtOAc: 10/1) to afford 2 (1.84 g, 90%) as white solid. 1H NMR (CDCl3, 300 MHz): delta 8.24 (d, J=1.5 Hz, 2H), 7.60 (dd, J=7.95, 1.65 Hz, 2H), 7.50 (d, J=7.95 Hz, 2H), 2.68 (s, 6H).
A. 4-lodo-2-nitro-benzoic acid.; In a 1 L three-neck round-bottom flask equipped with an internal thermometer, a reflux condenser, and an addition funnel, Bu4N+MnO4- (124 g, 343 mmol) was dissolved in pyridine (200 mL). The solution was heated to 60 C., and then the heating source was removed. A solution of <strong>[41252-97-5]4-iodo-2-nitrotoluene</strong> (43.0 g, 163 mmol) in pyridine (60 mL) was added through the additional funnel over2 h. The reaction temperature was maintained at 60 C. by adjusting the addition rate. When the addition was complete, the reaction mixture was cooled to rt. The solution was concentrated, diluted with EtOAc (300 mL) and water (200 mL), and stirred at rt for 30 min. The precipitated brown solid was filtered off and washed with EtOAc. The clear organic layer was washed with 5% aq. H2SO4 (200 mL) and brine (200 mL), dried (MgSO4), and concentrated to afford a thick, brown oil. The crude product was dissolved in EtOAc (200 mL) and then a solution of KOH (9.1 g, 163 mmol) in MeOH (ca. 30 mL) was added dropwise. The mixture was stirred at rt for 1 h, and the precipitated solid was collected by filtration and washed with EtOAc. The filtrate was concentrated and the precipitation was repeated with KOH in MeOH. The two crops were combined and dissolved in water (ca. 250 mL) and acidified with conc. HCl to pH<2. The precipitated white solid was collected by filtration and dried under vacuum to give the desired product (40 g, 136 mmol, 83%, >98% purity by HPLC). 1H NMR (400 MHz, CD3OD): 8.13 (d, J=1.6, 1H), 8.01 (dd, J=8.1, 1.6, 1H), 7.50 (d, J=8.1, 1H).
22%
Example 1: Synthesis of compounds of formula i; 2-Amino-4-methoxy-benzoic acid methyl ester; Step 1 : 4-Iodo-2-nitrobenzoic acid; To a mixture of <strong>[41252-97-5]4-iodo-2-nitrotoluene</strong> (9.0 g, 34 mmol) in H2O (340 mL) was added KMnO4 (22.0 g, 139 mmol). The mixture was heated at reflux for 5 h and then cooled to rt and filtered through Celite. The filtrate was acidified to pH=2 with cone. HCl. The precipitate that formed and was filtered and dried to give 4-iodo-2-nitrobenzoic acid (2.0 g, 20%). The filtrate was extracted with DCM (3 x 200 mL). The organic solutions were combined, dried over Na2SO4, filtered, and concentrated to provide a second lot of 4-iodo-2-nitrobenzoic acid (0.18 g, 2%).
20%
With potassium permanganate; In water; for 5h;Heating / reflux;
A. 4-Iodo-2-nitrobenzoic acid 4-Iodo-2-nitrotoluene (9.0 g, 34.2 mmol), KMnO4 (22.0 g, 139 mmol) and water (340 mL) were heated at reflux for 5 h. The resulting brown suspension of MnO2 was filtered off through a pad of diatomaceous earth, and the filter cake was washed with water. The basic filtrate was acidified with concentrated HCl causing crystallization of the desired acid. The crystals were collected by suction filtration and dried affording 1.86 g of the acid. The mother liquor was extracted with DCM (3*200 mL), and the combined extracts were dried (Na2SO4) and concentrated in vacuo to afford an additional 0.16 g of the benzoic acid. Total yield=2.02 g (20%). 1H NMR (400 MHz, CD3OD): 8.13 (d, J=1.6 Hz, 1H), 8.01 (dd, J=8.1, 1.6 Hz, 1H), 7.50 (d, J=8.1 Hz, 1H).
20%
A. 4-Iodo-2-nitrobenzoic acid. 4-Iodo-2-nitrotoluene (9.0 g, 34 mmol), KMnO4 (22.0 g, 139 mmol), and H2O (340 mL) were heated at reflux for 5 h. The resulting brown suspension was filtered through a pad of diatomaceous earth, and the filter cake was washed with H2O. The basic filtrate was acidified with concentrated HCl causing precipitation of the desired acid. The solid was collected by suction filtration and dried, affording 1.86 g of the acid. The mother liquor was extracted with DCM (3*200 mL), and the combined extracts were dried (Na2SO4) and concentrated in vacuo to afford an additional 0.16 g of the benzoic acid (total 2.02 g, 20%). 1H NMR (400 MHz, CD3OD): 8.13 (d, J=1.6 Hz, 1H), 8.01 (dd, J=8.1, 1.6 Hz, 1H), 7.50 (d, J=8.1 Hz, 1H).
20%
A. 4-Iodo-2-nitrobenzoic acid. ; 4-Iodo-2-nitrotoluene (9.0 g, 34.2 mmol), KMnO4(22.0 g, 139 mmol) and water (340 mL) were heated at reflux for 5 h. The resulting brown suspension was filtered through a pad of diatomaceous earth, washing with water. The basic filtrate was acidified with conc. HCl. The resulting solids were collected by suction filtration and dried to afford 1.86 g of the acid. The mother liquor was extracted with DCM (3×), and the combined extracts were dried (Na2SO4) and concentrated to afford an additional 0.16 g of the benzoic acid. Total yield=2.02 g (20%). 1H NMR (400 MHz, CD3OD): 8.13 (d, J=1.6, 1H), 8.01 (dd, J=8.1, 1.6, 1H), 7.50 (d, J=8.1, 1H).
With phenyllithium;tetrakis(triphenylphosphine) palladium(0); Zinc chloride; In tetrahydrofuran; cyclohexane;
EXAMPLE 2 This Example illustrates the preparation of (Z)-methyl 3-methoxy-2-[6-phenylindol-1-yl]acrylate (Compound No. 3 of Table I). Phenyllithium (10 ml of a 2.0M solution in a 7:3 mixture of cyclohexane and ether, 20 mmol) was added dropwise to zinc chloride (20 ml of a 1.0M solution in ether, 20 mmol) at room temperature. The resulting mixture was stirred for 2 hours, then a solution of <strong>[41252-97-5]4-iodo-2-nitrotoluene</strong> (2.63 g, 10 mmol) in THF (20 ml) and tetrakis(triphenylphosphine)palladium (0.3 g, 0.26 mmol) were added successively. The reaction mixture was stirred for 3 hours then diluted with 0.5M hydrochloric acid (40 ml) and extracted with ether (3*70 ml). The ether extracts were washed with brine, dried, concentrated then purified by column chromatography using petrol (60-80 C.)-ethyl acetate (9:1) on silica gel to give 4-phenyl-2-nitrotoluene (1.8 g, 85% yield) as a yellow oil.
With potassium acetate; palladium diacetate; bis-diphenylphosphinomethane; In water; at 110℃;Sealed tube;
Pd(OAc)2 (11.3 mg, 5 mol%), 1,1-Bis(diphenylphosphino)methane (dppm) (19.2 mg, 5mol%), KOAc (294 mg, 3.0 equiv.), <strong>[41252-97-5]4-iodo-2-nitrotoluene</strong> 2a (316 mg, 1.2 equiv.), and 5-fluoroindole 1 (135 mg, 1.0 equiv.) were subsequently taken in a glass vial with screw-cap underair. Degassed H2O (2 mL) was added to it. The resultant reaction mixture was stirred in sealedcap at 110 C (silicon oil bath temperature). After maximum reaction conversion (monitored byTLC, 24 h), the mixture was cooled to room temperature. The reaction mixture was extractedwith EtOAc (2 × 30 mL). The combined organic layer was washed with water (2 × 10 mL), driedover Na2SO4, filtered and concentrated under reduced pressure. The filteration of crude reactionmixture on a short plug of silica-gel (60-120 mess size) was done. Next, to the crude reactionmixture containing compound 3a taken in a round bottomed flask, were added SnCl2.2H2O (1.8g, 8.0 equiv.), conc. aq. HCl (0.5 mL) and absolute ethanol (3 mL). The reaction mixture washeated at 70 C till the complete conversion (monitored by TLC, 45 min.). Upon completion ofthe reaction, the mixture was poured into cold water (10 mL) and 20% aq. NaOH was added to ittill pH 8. The reaction mixture was then extracted with EtOAc (2 × 30 mL). The combinedorganic layer was washed with water (2 × 10 mL), dried over Na2SO4, filtered and concentratedunder reduced pressure. The column chromatographic purification of crude mixture on silica-gel(60-120 mess size) provided 5-Fluoro-2-(3-amino-4-methyl)phenylindole (4a, 48 mg, 20 %yield).
With sodium azide; copper diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In dimethyl sulfoxide; at 95℃; for 4h;
1.0 mmol of <strong>[41252-97-5]p-methyl-m-nitrophenyl iodide</strong>,1.2 mmol sodium azide,0.15 mmol DBUAnd 0.1mmol of copper acetate were sequentially added to a reaction flask equipped with 3mL of dimethyl sulfoxide,The reaction mixture was stirred at 95 C for 4 h,TLC was followed until the reaction was complete,A few drops of aqueous ammonia were added to the reaction mixture,Then extracted with ethyl acetate (10 mL × 3),Then washed once with saturated saline,dry,Suction filtration,Remove the solvent,Purification by column chromatography gave the desired product,Yield 70%.
60%
With sodium azide; copper(II) acetate monohydrate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In dimethyl sulfoxide; at 95℃; for 4h;
General procedure: CAUTION: Azides are potentially explosive and so appropriateprecautions against blast must be taken when preparing, handlingand heating them. Reactions must be carried out on a small scale. A mixture of the aryl iodide (1.0 mmol), sodium azide (1.2 mmol),DBU (0.15 mmol) and Cu(OAc)2·H2O (0.1 mmol) in DMSO (3.0 mL)in a 10 mL flask was heated to 95 C (the temperature in the reaction flask was monitored) for 1.5-5.0 h. After the reaction was completed asjudged by TLC, the cooled mixture was poured into water (30 mL)containing several drops of ammonia. The resulting aqueous phase was extracted with ethyl acetate (3 × 30 mL). The combined organic phases were washed with brine (50 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was loaded on asilica gel column and eluted with petroleum ether (boiling range 60-90 C)/ethyl acetate to afford the product.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
