* 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.
With triethylamine In dichloromethane at 20℃; for 12 h;
A solution of triethylamine (24 g, 237.6 mmol) and di-tert-butyl dicarbonate (20.75 g, 95.07 mmol) was added to a solution of 3-iodo-lH-indole (23.1 g, 95.05 mmol) in dichloromethane (200 mL) , Stirring at room temperature for 12 hours, TLC detection of raw materials disappeared. Add water, ethyl acetate extraction, combined organic phase, anhydrous sodium sulfate drying, The solvent was removed by rotary evaporation to give the product (27.7 g, yield 85percent).
82%
With dmap In dichloromethane at 20℃; for 1 h;
To a solution of 9 (2Og, 82mmol) in 2OmL of dry DCM was added Boc2O (2.7mg, 12.Ommoi) and DMAP (20mg, 0. i2mnmnol). The mixture was stirred at room temperature for ih. Then themixture was diluted with water (2OmL) and extracted with DCM (lOOmL). The organic layer was washed with brine (5OmL), dried over anhydrous Na2SO4, filtered and concentrated to dryness. The residue was purified by chromatograph column on silica gel to give product 10 (2.3g, yield: 82percent). 1HNMR (400 MHz, CDC1): c1.66 (s. 9 H), 7.297.40 (m. 3 H), 7.72. (s, I H), 8.12 (d, J=7.6 Hz, I H).
Reference：
[1] Organic Letters, 2018, vol. 20, # 7, p. 1978 - 1981
[2] Journal of Organic Chemistry, 2008, vol. 73, # 17, p. 6706 - 6710
[3] Tetrahedron, 2000, vol. 56, # 43, p. 8473 - 8480
[4] Patent: CN104876914, 2017, B, . Location in patent: Paragraph 0313-0315
[5] Patent: WO2017/173604, 2017, A1, . Location in patent: Page/Page column 19; 20
[6] Organic and Biomolecular Chemistry, 2011, vol. 9, # 14, p. 5129 - 5136
[7] European Journal of Organic Chemistry, 2011, # 24, p. 4532 - 4535
[8] European Journal of Organic Chemistry, 2013, # 21, p. 4564 - 4569
[9] Organic and Biomolecular Chemistry, 2013, vol. 11, # 36, p. 6113 - 6118
[10] Journal of Medicinal Chemistry, 1997, vol. 40, # 15, p. 2430 - 2433
[11] Organic letters, 2002, vol. 4, # 5, p. 815 - 817
[12] Chemistry - A European Journal, 2011, vol. 17, # 44, p. 12437 - 12443
[13] Chemical Communications, 2012, vol. 48, # 44, p. 5431 - 5433
[14] Organic Letters, 2013, vol. 15, # 6, p. 1346 - 1349
[15] Organic Letters, 2013, vol. 15, # 13, p. 3306 - 3309
2
[ 26340-47-6 ]
[ 39982-01-9 ]
[ 192189-07-4 ]
Yield
Reaction Conditions
Operation in experiment
92.11%
With dmap; triethylamine In dichloromethane at 20℃; for 1 h;
Indole (0.4681 g, 4.00 mmol) was iodinated by reacting with iodine (1 .0183 g, 4.01 mmol) and KOH (0.5666 g, 10.10 mmol) in DMF at room temperature for 3 h. The reaction was stopped by pouring the reaction mixture into 1 equivalent of sodium metabisulfite in iced water and adjusted the pH to 3 by 2N HC1. Then, it was filtered via buchner funnel, washed with water and dried to get yellow to brown solid (91.12percent). Then, the nitrogen atom in indole was protected with HOC protecting group by reacting with HOC anhydride (0.8750 g, 4.01 mmol), Et3N (1.1050 g, 10.92 mmol), and DMAP (0.0452 g, 0.37 mmol) in CH2C12 at room temperature for 1 h. The reaction mixture was extracted with 5percent sodium metabisulfite and dried over MgSO4 anhydrous before purification by column chromatography (5percent EtOAc in hexane) to obtain yellow solid (92.11percent). Tbe Sonogasbira reaction as described above was performed and purified by column chromatography (5percent EtOAc in hexane) to obtain brown liquid (96.77percent). The HOCwas deprotected by adding MeCN and water in 1 to 1 ratio into the intermediate compound (0.2419 g, 0.77 mmol) and activated with microwave generator at 1000 C. for 1 h. Then, it was extracted with CH2C12 and purified by column chromatography (10percent EtOAc in hexane) to obtain yellow liquid (72.86percent). Then, it was desilylated by K2C03 (0.1526 g, 1.10 mmol) in CH3OH for 2 h. The solvent was evaporated and the crude product was added CH2C12 and water. The pH was adjusted to 3 by 2N HC1 and extracted with CH2C12 before purification by column chromatography (10percent EtOAc in hexane to EtOAc) to give a pale yellow solid compound(41.70percent).
Reference：
[1] Patent: US2018/244653, 2018, A1, . Location in patent: Paragraph 0212
[2] Angewandte Chemie - International Edition, 2011, vol. 50, # 25, p. 5687 - 5690
With dmap; triethylamine; In dichloromethane; at 20℃; for 1h;
Indole (0.4681 g, 4.00 mmol) was iodinated by reacting with iodine (1 .0183 g, 4.01 mmol) and KOH (0.5666 g, 10.10 mmol) in DMF at room temperature for 3 h. The reaction was stopped by pouring the reaction mixture into 1 equivalent of sodium metabisulfite in iced water and adjusted the pH to 3 by 2N HC1. Then, it was filtered via buchner funnel, washed with water and dried to get yellow to brown solid (91.12%). Then, the nitrogen atom in indole was protected with HOC protecting group by reacting with HOC anhydride (0.8750 g, 4.01 mmol), Et3N (1.1050 g, 10.92 mmol), and DMAP (0.0452 g, 0.37 mmol) in CH2C12 at room temperature for 1 h. The reaction mixture was extracted with 5% sodium metabisulfite and dried over MgSO4 anhydrous before purification by column chromatography (5% EtOAc in hexane) to obtain yellow solid (92.11%). Tbe Sonogasbira reaction as described above was performed and purified by column chromatography (5% EtOAc in hexane) to obtain brown liquid (96.77%). The HOCwas deprotected by adding MeCN and water in 1 to 1 ratio into the intermediate compound (0.2419 g, 0.77 mmol) and activated with microwave generator at 1000 C. for 1 h. Then, it was extracted with CH2C12 and purified by column chromatography (10% EtOAc in hexane) to obtain yellow liquid (72.86%). Then, it was desilylated by K2C03 (0.1526 g, 1.10 mmol) in CH3OH for 2 h. The solvent was evaporated and the crude product was added CH2C12 and water. The pH was adjusted to 3 by 2N HC1 and extracted with CH2C12 before purification by column chromatography (10% EtOAc in hexane to EtOAc) to give a pale yellow solid compound(41.70%).
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