* 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 potassium iodate; sulfuric acid; water; iodine In acetic acid at 80℃; for 24 h; Inert atmosphere
4a (2.500 g, 10.2 mmol), I2 (1.085 g, 4.3 mmol) and KIO3 (0.545 g, 2.5 mmol) were dissolved in a mixture of AcOH (42.5 mL), H2O (2 mL) and H2SO4 (1 mL). After being stirred at 80 °C for 24 h under a nitrogen atmosphere, the reaction mixture was extracted with CH2Cl2 (3 * 50 mL) and washed with AcOH (3 * 50 mL), H2O (2 * 50 mL). The combined organic extracts were dried over anhydrous MgSO4 and concentrated under vacuum. The residue was recrystallized from CH2Cl2 to afford the title compound 10. Yield 97percent; White solid; M.p. 193-194 °C. 1H NMR (400 MHz, CDCl3): δ 3.83 (s, 2H), 7.47-7.51 (m, 2H), 7.59 (d, J = 8.0 Hz, 1H), 7.65-7.70 (m, 2H), 7.86 (s, 1H). 13C NMR (100 MHz, CDCl3): δ 36.75, 92.61, 121.56, 121.85, 128.57, 130.46, 134.54, 136.33, 140.12, 140.63, 144.94, 145.34.
95%
Stage #1: at 40 - 45℃; for 0.5 h; Stage #2: With potassium iodate; sulfuric acid; iodine In water at 20 - 60℃; for 4 h;
A. Synthesis of Intermediate 20 [0204] A 3-neck flask was charged with 2-bromofluorene (100 g) and acetic acid (2100 g). The contents were heated to 40-45° C. and agitated for approximately 30 minutes to obtain a clear solution. After adjusting the internal temperature to 20-30° C., 20percent (v/v) aq. H2SO4 (200 g, prepared with 64.0 g of H2SO4 and 136 g of water) was added, followed by I2 (53.0 g, 0.512 mole equiv) followed by KIO3 (17.5 g, 0.200 mole equiv). The slurry was heated at 58° C. (56-60° C.) for about 4 hours. The slurry was then cooled to 20-25° C. and a 9percent Na2SO3 solution (Na2SO3, 47.0 g; water, 500 g) was charged to the reaction mixture while maintaining the internal temperature at 20-30° C. The slurry was agitated at 25° C. for 1 hour and filtered. The filter cake was rinsed with 85 wt percent HOAc (200 g, prepared with 170 g of HOAc and 30 g of water), followed by water (200 g, 2.0 wt equiv). The filter cake was discharged and slurry-washed in water (1500 g) for about 1 hour, then filtered and rinsed with water until pH of the rinse is 6-7, and further rinsed with heptanes (200 g). The solids were dried under vacuum producing 143 g (95percent yield, 96percent AN purity by HPLC) of the product 20 as a white solid.
95%
With potassium iodate; sulfuric acid; iodine; acetic acid In water at 56 - 60℃; for 4 h;
A. Synthesis of Intermediate 20 [0240] A 3-neck flask was charged with 2-bromofluorene (100 g) and acetic acid (2100 g). The contents were heated to 40-45° C. and agitated for approximately 30 minutes to obtain a clear solution. After adjusting the internal temperature to 20-30° C., 20percent (v/v) aq. H2SO4 (200 g, prepared with 64.0 g of H2SO4 and 136 g of water) was added, followed by I2 (53.0 g, 0.512 mole equiv) followed by KIO3(17.5 g, 0.200 mole equiv). The slurry was heated at 58° C. (56-60° C.) for about 4 hours. The slurry was then cooled to 20-25° C. and a 9percent Na2SO3 solution (Na2SO3, 47.0 g; water, 500 g) was charged to the reaction mixture while maintaining the internal temperature at 20-30° C. The slurry was agitated at 25° C. for 1 hour and filtered. The filter cake was rinsed with 85 wt percent HOAc (200 g, prepared with 170 g of HOAc and 30 g of water), followed by water (200 g, 2.0 wt equiv). The filter cake was discharged and slurry-washed in water (1500 g) for about 1 hour, then filtered and rinsed with water until pH of the rinse is 6-7, and further rinsed with heptanes (200 g). The solids were dried under vacuum producing 143 g (95percent yield, 96percent AN purity by HPLC) of the product 20 as a white solid.
82%
With sulfuric acid; iodine; iodic acid In water; acetic acid at 85℃; for 4 h;
Compound D (40g, 0.16mop, iodine (16.9g, 0.066mop, iodic acid (6.89g, 0.039moq were added to the two-neck flask. distilled water (30mp, acetic acid (600mL), and sulfuric acid (14.4mL) were added and the mixture was slimed at 85C for 4 hoots. Upon completion of the reaction, the mixture was completely cooled to room temperature and washed with acetic acid and distilled water. Pure Compound E (49g, 82percent) was obtained by filtration.
79%
at 80 - 90℃; for 2 h;
EXAMPLE 7 2-Bromo-7-iodofluorene A mixture of 2-bromofluorene (12.61 g, 50 mmol), acetic acid (125 ML), water (9 ML), concentrated sulfuric acid (4 ML), iodine (5.1 g, 20.1 mmol) and iodic acid (2.2 g, 12.5 mmol) was heated at 80-90° C. for 2 hours, cooled and filtered.. The solids were washed with acetic acid (100 ML) and water (500 ML), to get the product 14.7 g (79percent yield), m.p. 179-185° C. Mass Spec. (m/z): 418 (M+ diiodo), 370, 372 (M+iodobromo), 322, 324, 326 (M+ dibromo).
4.37 g
at 80℃; for 24 h;
4.0 g of 2-bromofluorene was added, dispersed in 175 mL of glacial acetic acid,16 mL of 20percent sulfuric acid, 0.7 g of potassium iodate, 2.24 g of elemental iodine,The reaction was heated at 80 ° C for 24 hours. Close the heating, ice bath cooling reaction, add cold water 165mL dilution reaction mixture, filter, filter cake with tap water to the filtrate colorless.The resulting solid was collected, dried overnight at 60 ° C,40 mL of a 10: 1 (by volume) mixture of dichloromethane and methanol,60 ° C oil bath heating under the mixing beating 1 hour,Natural cooling overnight, pumping filter,The solid was vacuum dried at 60 ° C overnight to give compound 2 as a white solid (4.37 g).
Reference：
[1] Journal of Fluorine Chemistry, 2015, vol. 178, p. 195 - 201
[2] Patent: US2013/324740, 2013, A1, . Location in patent: Paragraph 0203; 0204
[3] Patent: US2013/324496, 2013, A1, . Location in patent: Paragraph 0239-0240
[4] Chemical Communications, 2002, # 15, p. 1608 - 1609
[5] Patent: WO2011/105700, 2011, A1, . Location in patent: Page/Page column 19; 20
[6] Journal of Materials Chemistry, 2012, vol. 22, # 15, p. 7515 - 7528
[7] Tetrahedron, 2007, vol. 63, # 36, p. 8881 - 8890
[8] Patent: US6730793, 2004, B1, . Location in patent: Page column 5
[9] Chemical Communications, 2009, # 33, p. 4950 - 4952
[10] Journal of Organic Chemistry, 2014, vol. 79, # 16, p. 7342 - 7357
[11] Journal of the Indian Chemical Society, 1938, vol. 15, p. 72,76
[12] Journal of the Indian Chemical Society, 1938, vol. 15, p. 72,76
[13] Patent: WO2006/114921, 2006, A1, . Location in patent: Page/Page column 74-77
[14] Patent: EP2085382, 2009, A1, . Location in patent: Page/Page column 39
[15] Patent: US2011/54229, 2011, A1, . Location in patent: Page/Page column 18
[16] Journal of Polymer Science, Part A: Polymer Chemistry, 2011, vol. 49, # 24, p. 5339 - 5349
[17] Journal of Materials Chemistry, 2012, vol. 22, # 23, p. 11816 - 11825
[18] Patent: CN106117187, 2016, A, . Location in patent: Paragraph 0058; 0059; 0060
[19] Patent: CN107879908, 2018, A, . Location in patent: Paragraph 0032-0035; 0057; 0078
2
[ 1133-80-8 ]
[ 7664-93-9 ]
[ 123348-27-6 ]
Yield
Reaction Conditions
Operation in experiment
79%
With iodine; iodic acid; acetic acid In water
EXAMPLE 2 2- Bromo-7- iodofluorene A mixture of 2-bromofluorene (12.61 g, 50 mmol), acetic acid (125 mL), water (9 mL), concentrated sulfuric-acid (4 mL), iodine (5.1 g, 20.1 mmol) and iodic acid (2.2 g, 12.5 mmol) was heated at 80-90° C. for 2 hours, cooled and filtered. The solids were washed with acetic acid (100 mL) and water (500 mL), to yield the product 14.7 g (79percent yield), m.p. 179-185° C. Mass Spec: m/z 418 (M+diiodo), 370, 372 (M+iodobromo), 322, 324,326 (M+dibromo).
With potassium iodate; sulfuric acid; iodine; acetic acid; In water; at 80℃; for 12h;Inert atmosphere;
2-bromoindole (2.44 g, 10 mmol), iodine (1.1 g, 4.5 mmol) and potassium iodate (0.65 g, 3 mmol) were dissolved in a mixed solvent (45 ml of glacial acetic acid, 5 ml of water and 2 ml of sulfuric acid). Under nitrogen protection, the reaction system was heated to 80 C for 12 h. After the reaction was completed, the reaction system was slowly cooled to room temperature, extracted with 10 ml of dichloromethane, and washed with water until neutral. The organic layer was dried over anhydrous sodium sulfate and filtered.The filtrate is recovered under reduced pressure,Residue column chromatography gave a white solid 3.63 g, yield 98%.
97%
With potassium iodate; sulfuric acid; water; iodine; In acetic acid; at 80℃; for 24h;Inert atmosphere;
4a (2.500 g, 10.2 mmol), I2 (1.085 g, 4.3 mmol) and KIO3 (0.545 g, 2.5 mmol) were dissolved in a mixture of AcOH (42.5 mL), H2O (2 mL) and H2SO4 (1 mL). After being stirred at 80 C for 24 h under a nitrogen atmosphere, the reaction mixture was extracted with CH2Cl2 (3 * 50 mL) and washed with AcOH (3 * 50 mL), H2O (2 * 50 mL). The combined organic extracts were dried over anhydrous MgSO4 and concentrated under vacuum. The residue was recrystallized from CH2Cl2 to afford the title compound 10. Yield 97%; White solid; M.p. 193-194 C. 1H NMR (400 MHz, CDCl3): delta 3.83 (s, 2H), 7.47-7.51 (m, 2H), 7.59 (d, J = 8.0 Hz, 1H), 7.65-7.70 (m, 2H), 7.86 (s, 1H). 13C NMR (100 MHz, CDCl3): delta 36.75, 92.61, 121.56, 121.85, 128.57, 130.46, 134.54, 136.33, 140.12, 140.63, 144.94, 145.34.
95%
A. Synthesis of Intermediate 20 [0204] A 3-neck flask was charged with 2-bromofluorene (100 g) and acetic acid (2100 g). The contents were heated to 40-45 C. and agitated for approximately 30 minutes to obtain a clear solution. After adjusting the internal temperature to 20-30 C., 20% (v/v) aq. H2SO4 (200 g, prepared with 64.0 g of H2SO4 and 136 g of water) was added, followed by I2 (53.0 g, 0.512 mole equiv) followed by KIO3 (17.5 g, 0.200 mole equiv). The slurry was heated at 58 C. (56-60 C.) for about 4 hours. The slurry was then cooled to 20-25 C. and a 9% Na2SO3 solution (Na2SO3, 47.0 g; water, 500 g) was charged to the reaction mixture while maintaining the internal temperature at 20-30 C. The slurry was agitated at 25 C. for 1 hour and filtered. The filter cake was rinsed with 85 wt % HOAc (200 g, prepared with 170 g of HOAc and 30 g of water), followed by water (200 g, 2.0 wt equiv). The filter cake was discharged and slurry-washed in water (1500 g) for about 1 hour, then filtered and rinsed with water until pH of the rinse is 6-7, and further rinsed with heptanes (200 g). The solids were dried under vacuum producing 143 g (95% yield, 96% AN purity by HPLC) of the product 20 as a white solid.
95%
With potassium iodate; sulfuric acid; iodine; acetic acid; In water; at 56 - 60℃; for 4h;
A. Synthesis of Intermediate 20 [0240] A 3-neck flask was charged with 2-bromofluorene (100 g) and acetic acid (2100 g). The contents were heated to 40-45 C. and agitated for approximately 30 minutes to obtain a clear solution. After adjusting the internal temperature to 20-30 C., 20% (v/v) aq. H2SO4 (200 g, prepared with 64.0 g of H2SO4 and 136 g of water) was added, followed by I2 (53.0 g, 0.512 mole equiv) followed by KIO3(17.5 g, 0.200 mole equiv). The slurry was heated at 58 C. (56-60 C.) for about 4 hours. The slurry was then cooled to 20-25 C. and a 9% Na2SO3 solution (Na2SO3, 47.0 g; water, 500 g) was charged to the reaction mixture while maintaining the internal temperature at 20-30 C. The slurry was agitated at 25 C. for 1 hour and filtered. The filter cake was rinsed with 85 wt % HOAc (200 g, prepared with 170 g of HOAc and 30 g of water), followed by water (200 g, 2.0 wt equiv). The filter cake was discharged and slurry-washed in water (1500 g) for about 1 hour, then filtered and rinsed with water until pH of the rinse is 6-7, and further rinsed with heptanes (200 g). The solids were dried under vacuum producing 143 g (95% yield, 96% AN purity by HPLC) of the product 20 as a white solid.
82%
With sulfuric acid; iodine; iodic acid; In water; acetic acid; at 85℃; for 4h;
Compound D (40g, 0.16mop, iodine (16.9g, 0.066mop, iodic acid (6.89g, 0.039moq were added to the two-neck flask. distilled water (30mp, acetic acid (600mL), and sulfuric acid (14.4mL) were added and the mixture was slimed at 85C for 4 hoots. Upon completion of the reaction, the mixture was completely cooled to room temperature and washed with acetic acid and distilled water. Pure Compound E (49g, 82%) was obtained by filtration.
79%
With sulfuric acid; iodine; iodic acid; acetic acid; at 80 - 90℃; for 2h;
EXAMPLE 7 2-Bromo-7-iodofluorene A mixture of 2-bromofluorene (12.61 g, 50 mmol), acetic acid (125 ML), water (9 ML), concentrated sulfuric acid (4 ML), iodine (5.1 g, 20.1 mmol) and iodic acid (2.2 g, 12.5 mmol) was heated at 80-90 C. for 2 hours, cooled and filtered.. The solids were washed with acetic acid (100 ML) and water (500 ML), to get the product 14.7 g (79% yield), m.p. 179-185 C. Mass Spec. (m/z): 418 (M+ diiodo), 370, 372 (M+iodobromo), 322, 324, 326 (M+ dibromo).
Under an atmospheric argon gas flow, dissolving 12.5 g of 2-bromofluorene into 50 ml of acetic acid, 0.9 ml of sulfuric acid was dripped and stirred at a room temperature for 10 min. Subsequently, 6.5 g of iodine and 2.33 g of periodic acid were added and the reaction was allowed to proceed at 80 C for 6 h. The resultant solution was cooled down, extracted through toluene and tap water. Subsequently, a toluene layer was washed with sodium bicarbonate water, saturated sodium chloride solution and tap water, and then dried over sodium sulfate. After the sodium sulfate was separated by filtration, purifying the resultant solid by means of a silicagel chromatography (toluene), the solid was washed with n-hexane and vacuum dried to obtain 9.00 g of solid, which was analyzed by FD-MS and identified as Intermediate 4.
With sulfuric acid; iodine; iodic acid; acetic acid; In water; at 85℃; for 12h;
In acetic acid (250 mL), dissolved were 2,7-dibromofluorene (20 g, 810 mmol), iodine (9.3 g, 360 mmol) and iodic acid (3.58 g, 20 mmol). To the solution, distilled water (15 mL) and sulfuric acid (7.5 mL) were added, and the mixture was stirred at 85 C. under reflux for 12 hours. After cooling to ambient temperature, the solid was filtered under reduced pressure, and washed subsequently with distilled water (300 mL), saturated aqueous potassium carbonate solution (300 mL), methanol (300 mL) and hexane (400 mL). Drying the solid under reduced pressure gave Compound (129) (19 g, 530 mmol).
4.37 g
With potassium iodate; sulfuric acid; iodine; acetic acid; at 80℃; for 24h;
4.0 g of 2-bromofluorene was added, dispersed in 175 mL of glacial acetic acid,16 mL of 20% sulfuric acid, 0.7 g of potassium iodate, 2.24 g of elemental iodine,The reaction was heated at 80 C for 24 hours. Close the heating, ice bath cooling reaction, add cold water 165mL dilution reaction mixture, filter, filter cake with tap water to the filtrate colorless.The resulting solid was collected, dried overnight at 60 C,40 mL of a 10: 1 (by volume) mixture of dichloromethane and methanol,60 C oil bath heating under the mixing beating 1 hour,Natural cooling overnight, pumping filter,The solid was vacuum dried at 60 C overnight to give compound 2 as a white solid (4.37 g).
With potassium iodate; sulfuric acid; iodine; acetic acid; at 20 - 56℃; for 3.5h;
LD-G and acetic acid were added to the reactor, heated to 40C, stirred for 25 minutes, and dissolved. After adjusting the reactor temperature to 20C, 18% sulfuric acid was added, followed by iodine, potassium iodate The reaction was heated at 56 C for 3.5 h. The reaction was monitored by HPLC. The reaction was then cooled to 20 C. 8% sodium sulfite solution was added to the reaction mixture. The temperature was maintained at 20 C and stirring was continued for 0.5 h. , Centrifugation, the filter cake was washed with water and dried to give a solid product LD-H
With sulfuric acid; iodine; acetic acid; In water;
(1) Synthesis of 2-bromo-7-iodofluorene Charged were 2-bromofluorene 25.0 g, iodine 11.5 g, orthoperiodic acid 4.88 g, acetic acid 150 ml, conc. sulfuric acid 3 ml and water 10 ml, and the mixture was heated at 60 C. for 30 minutes while stirring. Further, the temperature was elevated up to 90 C., and the mixture was heated for 3 hours while stirring. The reaction solution was left cooling down to room temperature and poured into 500 ml of water. The precipitate formed was filtered and washed with ethanol and water. The solid matter thus obtained was recrystallized from ethanol to obtain 26.5 g of yellow crystal of 2-bromo-7-iodofluorene.
With potassium hydroxide; potassium iodide; In dimethyl sulfoxide;
EXAMPLE 3 2-Bromo-7-iodo-9,9-didecylfluorene To a mechanically stirred mixture of 7-iodo-2-bromofluorene (from example 2; 41.34 g, 0.1114 mol), DMSO (100 mL), potassium iodide (1.7 g), and powdered potassium hydroxide (28 g) cooled in a cold water bath, 1-bromodecane (53 mL) was added dropwise, and the mixture was stirred for 24 hours. The oil that separated on dilution with water, was extracted with toluene. Toluene extract was washed with water, dried and concentrated. The residual oil was passed through a column of 300 g alumina. Elution with 900 mL hexanes gave the product as an oil, 65 g This was left in 200 mL of isopropanol, when the product solidified, 58.63 g (81% yield), m.p. 43-45 C. Mass Spec.: m/z 698 (M+diiodo), 650,652 (M+).
81%
With potassium hydroxide; potassium iodide; In dimethyl sulfoxide; for 24h;
EXAMPLE 8 2-Bromo-7-iodo-9,9-didecylfluorene To a mechanically stirred mixture of 7-iodo-2-bromofluorene (example 2; 41.34 g, 0.1 114 mol), DMSO (100 ML), potassium iodide (1.79 g), and powdered potassium hydroxide (28 g) cooled in a cold water bath, 1-bromodecane (53 ML) was added dropwise, and the mixture was stirred for 24 hours.. The oil that separated on dilution with water, was extracted with toluene.. toluene extract was washed with water, dried and concentrated.. The residual oil was passed through a column of 300 g alumina.. Elution with 900 ML hexanes gave the product as an oil, 65 g.. This was left in 200 ML of isopropanola when the product solidified, 58.63 g (81% yield), m.p. 43-45 C. Mass Spec. (m/z): 698 (M+ diiodo), 650, 652 (M+).
EXAMPLE 2 2- Bromo-7- iodofluorene A mixture of 2-bromofluorene (12.61 g, 50 mmol), acetic acid (125 mL), water (9 mL), concentrated sulfuric-acid (4 mL), iodine (5.1 g, 20.1 mmol) and iodic acid (2.2 g, 12.5 mmol) was heated at 80-90 C. for 2 hours, cooled and filtered. The solids were washed with acetic acid (100 mL) and water (500 mL), to yield the product 14.7 g (79% yield), m.p. 179-185 C. Mass Spec: m/z 418 (M+diiodo), 370, 372 (M+iodobromo), 322, 324,326 (M+dibromo).
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; In water; dimethyl sulfoxide;
(2) Synthesis of 2-bromo-7-iodo-9,9-dimethylfluorene A reaction vessel was charged with <strong>[123348-27-6]2-bromo-7-iodofluorene</strong> 26.5 g, dimethylsulfoxide (DMSO) 100 ml, benzyltriethylammonium chloride 0.500 g and a sodium hydroxide aqueous solution 100 g of 50% by weight under Ar atmosphere. This reaction vessel was put in a water bath, and methyl iodide 22.3 g was added thereto. After carrying out reaction for 5 hours, 500 ml of water was added thereto, and the resulting precipitate was filtered. The solid matter obtained was washed with water and methanol to obtain 20.0 g of yellow crystal of 2-bromo-7-iodo-9,9-dimethylfluorene.
Under an atmospheric argon gas flow, 9.00 g of Intermediate 4 and 0.35 g of benzyltriethylammonium chloride were placed into 25 ml of DMSO (dimethylsulfoxide) and 8 ml of 50 wt % NaOH aqueous solution and stirred at a room temperature for 10 min, and dripping 2.6 ml of methyl iodide, the reaction was allowed to proceed at a room temperature for 3 h. The resultant solution was extracted through toluene and tap water, washed with saturated sodium chloride solution and tap water, and condensed. Purifying by means of silicagel chromatography (n-hexane), vacuum dried to obtain 8.50 g of solid, which was analyzed by FD-MS and identified as Intermediate 5.
With potassium iodide; potassium hydroxide; In dimethyl sulfoxide; at 20℃; for 24h;
Compound (129) (19 g, 530 mmol), potassium iodide (0.85 g, 5.1 mmol) and potassium hydroxide (12.9 g, 230 mmol) were dissolved in DMSO (150 mL), and iodomethane (7.97 mL, 128 mmol) was added thereto at 10 C. The mixture was stirred at ambient temperature for 24 hours, and distilled water (200 mL) was added thereto. Filtering the solid under reduced pressure and washing with methanol (200 mL) gave Compound (130) (15 g, 370 mmol).
2-bromo-9,9-bis(2-ethylhexyl)-7-iodo-9H-fluorene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
With sodium hydroxide; In water; dimethyl sulfoxide; at 20℃; for 24h;Inert atmosphere;
10 (1.269 g, 3.37 mmol) and 3-(bromomethyl)heptane C8H17Br (1.660 g, 8.425 mmol) was added to a flask. Then DMSO (12.5 mL) and NaOH (aq.) (1.3 mL) were added to the mixture at rt. After being stirred at rt for 24 h under a nitrogen atmosphere, the reaction mixture was poured into ice (150 g) and extracted with AcOEt (2 * 100 mL). The organic extracts were dried over anhydrous MgSO4 and concentrated under vacuum. The residue was purified by flash chromatography (silica gel, petroleum ethter) to afford the crude product. Then the crude product was purified by flash chromatography (silica gel, petroleum ethter) to afford a pure title compound 11. Yield 77%; Yellowish sticky oil; 1H NMR (400 MHz, CDCl3): delta 0.43-0.94 (m, 30H), 1.92-1.97 (m, 4H), 7.40 (d, J = 8.0 Hz, 1H), 7.44 (dd, J = 8.0 Hz, 2.0 Hz, 1H), 7.47-7.49 (m, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.63-7.66 (m, 1H), 7.68-7.71 (m, 1H). 13C NMR (100 MHz, CDCl3): delta 10.63, 14.42, 23.09, 23.12, 27.44, 28.41, 33.98, 35.05, 44.61, 55.63, 121.43, 121.70, 127.69, 130.42, 133.76, 136.29, 139.58, 140.14, 152.51, 152.90.
With potassium iodide; potassium hydroxide; In dimethyl sulfoxide; at -10 - 20℃; for 9.5h;Inert atmosphere;
Compound E (49g 0.13mo1), KOH (33g, 0.60mo1), and KI (2.2g, 0.013mo1) were added to the one-neck flask, an argon atmosphere was established in a vacuum. DMSO(anhydrons) (SOOmI) was added and the mixture was stored at 0C for 10 minutes. After adding bTnmoethane (23mL, 0.30mo1) dropwise, the mixture was stirred at-10C for 30 minutes and then stirred at room temperature for 9 hours. Upon completion of the reaction, a solid produced by adding excess distilled water was filtered and the filtered solid was extracted with methylene chloride (MC). The organic layer was dried with MgSO, and the solvent was removed using a rotary evaporator. Pure Compound F (37g, 66%) was separated by column chromatography using hexane as an eluenr.
60%
With potassium iodide; potassium hydroxide; In dimethyl sulfoxide; at 10 - 20℃;Inert atmosphere;
A mixture of <strong>[123348-27-6]2-bromo-7-iodo-9H-fluorene</strong> (3.5 g, 9.43 mmol), potassium hydroxide (2.38 g,42.4 mmol), potassium iodide (0.16 g, 0.94 mmol) in DMSO (1.6 mL) was stirred at 10Cunder nitrogen condition. Bromoethane (1.6 mL, 21.7 mmol) was added dropwise. Then, themixture was stirred at room temperature for overnight. After confirming the progress of thereaction by TLC, the reaction is terminated by adding water, and the solid is collected througha filter. The crude product was purified by recrystallization from CH2Cl2:EtOH to give thedesired compound (2.43 g, 60%). 1H-NMR (CDCl3, 500 MHz) delta (ppm) 7.63-7.65 (m, 2H),7.51 (d, J =8.0 Hz, 1H), 7.38-7.45 (m, 3H), 1.97 (q, J = 7.2 Hz, 4H), 0.30 (t, J =7.2 Hz, 6H).
3-(7-((E)-2-(7-(bis(4-(2-(2-methoxyethoxy)ethoxy)phenyl)-amino)-9,9-bis(2-(2-methoxyethoxy)ethyl)-9H-fluoren-2-yl)vinyl)-9,9-bis(2-(2-methoxyethoxy)ethyl)-9H-fluoren-2-yl)-2-cyanoacrylic acid[ No CAS ]
B. Synthesis of Intermediate 21 [0207] The starting material (20, 100 g) and N-fluorobenzenesulfonimide (NFSI, 251 g, 2.95 mole equiv) were added as solids to a flask. To the mixture was added THF (1000 g) and with stirring the solids dissolved. The solution was degassed three times by slowly applying vacuum, followed by breaking vacuum with nitrogen. The solution was cooled in a -78 C. bath to an internal temp of -68 C. Upon cooling, a white to off-white slurry was formed. A solution of the base (1.0M LiHMDS in THF, 720 g, 3.00 mole equiv) was added at such a rate that the internal temperature was kept below -55 C. The internal temp was <-60 C. for the majority of the addition, total addition time was about 1 h. The reaction completion was monitored by HPLC analysis. The reaction was quenched by the addition of NH3/MeOH (7N NH3 in MeOH, 8 g) and the cold bath was removed. After the internal temperature had warmed to -20 C., HPLC analysis showed complete consumption of the excess N-fluorobenzenesulfonimide. The internal temperature was adjusted to 0 C. Heptanes (342 g) was added and the solution stirred for 10 minutes. If necessary, the temperature was adjusted to 20-25 C. The slurry was filtered and the solids rinsed with a mixture of THF/heptanes twice (for each rinse: THF, 89.0 g; heptanes: 205 g). The filtrate was stored at 5 C. (2-8 C.) for ca. 20 hours. The solution was then filtered into a flask and concentrated to 2.5-3.0 volumes under vacuum at maximum internal temperature of 35 C. CH2Cl2 (1500 g) was charged and the slurry agitated at reflux (ca. 40 C.) for 30 minutes. After adjusting the internal temperature to 20-25 C., the slurry was filtered through a pad of celite, and the filter cake was rinsed with DCM (400 g, 4.0 wt equiv). The filtrate was concentrated to about 3.0 volumes under vacuum. Methanol (600 g,) was added and the mixture was concentrated to about 4.0 volumes, additional methanol (300 g) was added and the mixture was concentrated again to about 4.0 volumes (300 volumes). The slurry was filtered and rinsed with methanol twice (for each rinse, 100 g). The product 21 was dried under vacuum producing 90 g (82% yield, 97-98% AN purity by HPLC) of the product as an off-white to pale yellow solid. 1H NMR (400 MHz, CDCl3, delta): 7.94 (d, J=1.2 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.74 (d, J=1.4 Hz, 1H), 7.60 (d, J=8.3 Hz, 1H), 7.41 (d, J=8.1 Hz, 1H), 7.29 (d, J=8.0 Hz, 1H). 19F NMR (376 MHz, CDCl3) delta -111.0 (s, 2F).
82%
B. Synthesis of Intermediate 21 [0242] The starting material (20, 100 g) and N-fluorobenzenesulfonimide (NFSI, 251 g, 2.95 mole equiv) were added as solids to a flask. To the mixture was added THF (1000 g) and with stirring the solids dissolved. The solution was degassed three times by slowly applying vacuum, followed by breaking vacuum with nitrogen. The solution was cooled in a -78 C. bath to an internal temp of -68 C. Upon cooling, a white to off-white slurry was formed. A solution of the base (1.0M LiHMDS in THF, 720 g, 3.00 mole equiv) was added at such a rate that the internal temperature was kept below -55 C. The internal temp was <-60 C. for the majority of the addition, total addition time was about 1 h. The reaction completion was monitored by HPLC analysis. The reaction was quenched by the addition of NH3/MeOH (7N NH3 in MeOH, 8 g) and the cold bath was removed. After the internal temperature had warmed to -20 C., HPLC analysis showed complete consumption of the excess N-fluorobenzenesulfonimide. The internal temperature was adjusted to 0 C. Heptanes (342 g) was added and the solution stirred for 10 minutes. If necessary, the temperature was adjusted to 20-25 C. The slurry was filtered and the solids rinsed with a mixture of THF/heptanes twice (for each rinse: THF, 89.0 g; heptanes: 205 g). The filtrate was stored at 5 C. (2-8 C.) for ca. 20 hours. The solution was then filtered into a flask and concentrated to 2.5-3.0 volumes under vacuum at maximum internal temperature of 35 C. CH2Cl2 (1500 g) was charged and the slurry agitated at reflux (ca. 40 C.) for 30 minutes. After adjusting the internal temperature to 20-25 C., the slurry was filtered through a pad of celite, and the filter cake was rinsed with DCM (400 g, 4.0 wt equiv). The filtrate was concentrated to about 3.0 volumes under vacuum. Methanol (600 g,) was added and the mixture was concentrated to about 4.0 volumes, additional methanol (300 g) was added and the mixture was concentrated again to about 4.0 volumes (300 volumes). The slurry was filtered and rinsed with methanol twice (for each rinse, 100 g). The product 21 was dried under vacuum producing 90 g (82% yield, 97-98% AN purity by HPLC) of the product as an off-white to pale yellow solid. 1H NMR (400 MHz, CDCl3, delta): 7.94 (d, J=1.2 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.74 (d, J=1.4 Hz, 1H), 7.60 (d, J=8.3 Hz, 1H), 7.41 (d, J=8.1 Hz, 1H), 7.29 (d, J=8.0 Hz, 1H). 19F NMR (376 MHz, CDCl3) delta -111.0 (s, 2F).
81%
With potassium hexamethylsilazane; N-fluorobis(benzenesulfon)imide; In tetrahydrofuran; at -78 - -60℃; for 3h;Inert atmosphere;
Take 2-bromo-7-iodonium (3.7 g, 10 mmol),N-Fluorobisbenzenesulfonamide (NFSI) (7.9 g, 25 mmol). Under a nitrogen atmosphere, 100 ml of THF was added, and the reaction liquid was cooled to -78 C, and a THF solution of bis-(trimethylsilyl)amine lithium (4.9 g, 30 mmol) was added dropwise, and the temperature was kept below -60 C during the dropwise addition. After the completion of the dropwise addition, the reaction was continued for 3 hours. After the reaction was completed, the reaction solution was quenched with NH3/CH3OH, the low temperature bath was removed, and turbidity appeared in the reaction system, filtered, washed with THF, and the filtrate was collected.Evaporation and evaporation, the residue was added to dichloromethane and stirred under reflux, filtered, and the filtrate was evaporated under reduced pressure.The solvent was beaten and filtered to obtain a yellow solid yield: 81 g, yield: 81%.
2.57 g
2 1.96 g of compound 2 and 6.66 g of N-fluorobisulfonamide were added to 40 mL of nitrogen Water tetrahydrofuran, the ice salt bath was cooled for 30 minutes, and then a solution of potassium tris Of tetrahydrofuran solution), dropping the natural temperature of 3h. The reaction solution was cooled in an ice bath and 0.1 mL of methanol was added dropwise Grade), adding n-hexane 40 mL to dilute the reaction solution. The above suspension was stirred for 30 minutes and then filtered, and the filter cake was oil Ether (50 mL x 3), the filtrate was collected and the column chromatography (petroleum ether) gave 3 m of a white solid (2.57 g).
With n-butyllithium; N-fluorobis(benzenesulfon)imide; In tetrahydrofuran; hexane; at -75 - -60℃; for 1.5h;Inert atmosphere;
into the reactor add tetrahydrofuran, LD-H, N-fluorobenzenesulfonimide (NFSI), the solid is dissolved with stirring and replaced with nitrogen three times, under nitrogen protection, the reaction solution is cooled at-75 C, keep temperature at below -60C and added the drops of butyl lithium n-hexane solution (1.0 M), dropping, controlling internal temperature at-60C, continue the reaction 1.5 (HPLC monitoring reaction completed), add methanol to quench the reaction, after adjusting the temperature at-22C, HPLC analysis showed complete consumption of excess N-oxobenzene carbimide, adjust the temperature at 0 C, add n-hexane, continue stirring for 20 minutes, filter, rinse the filter cake with n-hexane, the filtrate is concentrated under vacuum below 20C to 2.5 volumes, add dichloromethane, heat to reflux for 40 minutes, concentrate the mixture to 3.5 volumes, add additional methanol, and the solution is again concentrated at 3.5 volume, cool down, filter, and rinse twice with methanol, dry, and obtained the solid product LD-I.
With n-butyllithium; N-fluorobis(benzenesulfon)imide; In tetrahydrofuran; hexane; at -75 - -60℃;
Preparation Step: The reactor was added tetrahydrofuran, LD-H, N- fluorobenzene sulfonimide (NFSI), stirring the solid was dissolved, purged with nitrogen three times, under nitrogen, the reaction solution was cooled to -75 C, the temperature was maintained -60 C added butyllithium hexane solution (1.0M), dropwise to control the internal temperature of -60 C, the reaction was continued 1.5 (HPLC to monitor completion of the reaction), was added the reaction was quenched with methanol, adjusted after the temperature to -22 C, HPLC analysis showed an excess of N- oxobenzenebutanoic carbodiimide completely disappeared consumption, the temperature was adjusted to 0 C, was added n-hexane, stirring continued for 20 minutes, filtered, rinsed with n-hexane by filtration cake, the filtrate was 20 concentrated in vacuo to 2.5 volumes or less , dichloromethane was added and heated to reflux for 40 min, the mixture was concentrated to 3.5 volume, plus the additional methanol, and the solution was again concentrated to 3.5 volume, cooled, filtered, and Rinse twice with methanol and dry to give solid product LD-I.
With oxygen; lithium hexamethyldisilazane; In tetrahydrofuran; at 60℃; under 760.051 Torr; for 12h;Sealed tube; Green chemistry;
General procedure: To an 8 mL oven-dried vial, 4-benzylpyridine (0.1 mmol), dry THF (1 mL), LiHMDS (0.15mmol) were added subsequently. The reaction system was sealed by a rubber septum with a needleconnected with O2 balloon. After stirring at 60 C for 12 h, the reaction mixture was passed througha short pad of silica gel and eluted with ethyl acetate (1 mL × 3). The combined organics wereconcentrated under reduced pressure. The residue was purified by flash chromatography to givethe diarylketone 2a as white solid (15.6 mg, 85% yield).
85%
With chromium(VI) oxide; acetic anhydride; acetic acid; at 20℃; for 16h;
Compound 2 (6g) was suspended in acetic acid (30 mL) and acetic anhydride (30 mL) of the mixture, at room temperature was slowly added CrO3(6g). The mixture was stirred for 16h at room temperature, poured into water, neutralized with NaHCO 3After adjusting the pH to neutral, and filtered to give a yellow solid, this solid was then recrystallized from ethanol to obtain a yellow solid product (8) (5.3g, 85%).
With N-fluorobis(benzenesulfon)imide; lithium hexamethyldisilazane; In tetrahydrofuran; at -20℃; for 2h;
20 g of compound 1 and 18.70 g of NFSI were dissolved in 200 mL of THF and the temperature was lowered to -20 c, In the system to maintain the internal temperature of -20 C slowly dropping lmol / L LiHMDS solution to get 60ml of THF, The reaction was stirred for 2 hours, concentrated, filtered under water and dried in vacuo to give 16.53 g of compound 2 in a yield of 78.8%
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