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Stage #1: With oxalyl dichloride; dimethyl sulfate In dichloromethane at -78℃; for 1 h; Inert atmosphere Stage #2: With triethylamine In dichloromethane at -78 - 20℃; for 2 h; Inert atmosphere
To a solution of dimethyl sulfoxide (6.50 mL, 91.5 mmol) in CH2Cl2 (45 mL) was added oxalyl chloride (1.57 mL, 18.3 mmol) at -78 °C. The resulting mixture was stirred at the same temperature for 20 min. A solution of 13 (1.99 g, 9.15 mmol) in CH2Cl2 (10 mL) was added to the reaction flask. After stirring for 1 h, triethylamine (6.40 mL, 45.8 mmol) was then added. The reaction mixture was stirred at -78 °C for 1 h, warmed to room temperature, and then stirred for 1 h. The reaction was quenched with 1 N HCl, and the aqueous phase was then separated and extracted with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, and then concentrated in vacuo. Purification by silica gel column chromatography (hexane/EtOAc = 5/1) gave 15 (1.92 g, 8.93 mmol, 98percent) as a colorless powder;
With diisobutylaluminium hydride In tetrahydrofuran; hexane at -78 - 0℃; for 1 h; Inert atmosphere
To a solution of methyl 3-bromo-4-methoxybenzoate (12, 2.00 g, 8.16 mmol) in THF (20 mL) was added DIBAL–H (1.00 M in hexane, 20.4 mL) at −78 °C. The mixture was stirred at −78 °C for 30 min and 0 °C for 30 min. To the reaction mixture at −78 °C was added methanol (10 mL) dropwisely followed by saturated aqueous Rochelle salt solution (16 mL) and EtOAc (20 mL). After being stirred at room temperature for 2 h, the aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4, and then concentrated in vacuo. Purification on silica gel column chromatography (hexane/EtOAc=2:1) gave 13 (1.73 g, 7.96 mmol, 98percent) as a colorless solid; Rf 0.17 (hexane/EtOAc=3:1); 1H NMR (300 MHz, CDCl3) δ 7.57 (1H, d, J=2.2 Hz, H18), 7.27 (1H, dd, J=8.6, 2.2 Hz, H15), 6.88 (1H, d, J=8.6 Hz, H16), 4.61 (2H, s, H13), 3.90 (3H, s, OMe); 13C NMR (75 MHz, CDCl3) δ 55.5, 134.6, 132.4, 112.0, 111.8, 64.4, 56.4; EIMS (m/z) calcd for C8H9BrO2 [M]+ 215.98, found 216.05
Reference：
[1] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 18, p. 6874 - 6885
[2] Patent: JP2005/120047, 2005, A, . Location in patent: Page/Page column 106
[3] Chemical Communications, 1999, # 3, p. 287 - 288
[4] Tetrahedron Letters, 2013, vol. 54, # 21, p. 2737 - 2739
[5] Journal of the Chemical Society, 1938, p. 1780,1782
[6] Journal of the Chemical Society [Section] C: Organic, 1970, p. 2234 - 2238
[7] Patent: US6582351, 2003, B1,
[8] Chemical Communications, 2014, vol. 50, # 40, p. 5254 - 5257
[9] Patent: CN106632070, 2017, A, . Location in patent: Paragraph 0024-0025
4
[ 443776-91-8 ]
[ 38493-59-3 ]
Reference：
[1] Synthesis, 2005, # 4, p. 547 - 550
5
[ 621-59-0 ]
[ 38493-59-3 ]
Reference：
[1] Synthesis, 2005, # 4, p. 547 - 550
6
[ 157790-73-3 ]
[ 38493-59-3 ]
Reference：
[1] Synthesis, 2005, # 4, p. 547 - 550
7
[ 105-13-5 ]
[ 104-92-7 ]
[ 38493-59-3 ]
[ 123-11-5 ]
Reference：
[1] Journal of Organic Chemistry, 2000, vol. 65, # 12, p. 3880 - 3881
With sodium borohydrid; In tetrahydrofuran; ethanol;
PREPARATION 31 To a solution of 3-bromo-4-methoxybenzaldehyde (4.98 g) in ethanol (50 mL) and tetrahydrofuran (10 mL) was added sodium borohydride (1.31 g) under ice-water cooling. The mixture was stirred at 0° C. for 2 hours. After evaporation of the solvent, the residue was partitioned between ethyl acetate and water. The separated organic layer was washed successively with water and brine, and dried over magnesium sulfate. The organic layer was evaporated in vacuo to give 3-bromo-4-methoxybenzyl alcohol as a colorless oil (4.98 g). NMR(CDCl3, delta): 1.73 (1H, t, J=7 Hz), 3.90 (3H, s), 4.60 (2H, d, J=7 Hz), 6.88 (1H, d, J=8 Hz), 7.25 (1H, dd, J=4, 8 Hz), 7.56 (1H, d, J=4 Hz).
With sodium tetrahydroborate; ethanol;
(1) 30 g of raw material A, 3-bromo-4-methoxybenzaldehyde was taken, and NaOH4 8-10 g was slowly added in batches and reacted in ethanol. The reaction was monitored by TLC. After completion of the reaction, the ethanol was removed, and the combined organic phases were dried over anhydrous sodium sulfate and dried to give 30.0 g of 3-bromo-4-methoxybenzyl alcohol as a white product. The product was subjected to the next step without further purification Rate> 98percent
To a solution of <strong>[38493-59-3](3-bromo-4-methoxyphenyl)-methanol</strong> (13, 504 mg, 2.32 mmol) in CH2Cl2 (10 mL) was added triphenylposphine (1.23 g, 4.60 mmol) at room temperature. After being stirred at room temperature for 10 min, carbon tetrabromide (1.53 g, 4.61 mmol) was added at -78 C, and being stirred at -78 C for 2 h. The reaction mixture was treated with 50% hexane/EtOAc mixture (20 mL), and passed through short silica gel column chromatography (50% hexane/EtOAc, 200 mL). Purification by silica gel column chromatography (hexane/EtOAc=5:1) gave 14 (537 mg, 1.92 mmol, 83%) as a colorless solid; Rf 0.60 (hexane/EtOAc=3:1); 1H NMR (300 MHz, CDCl3) delta 7.59 (1H, d, J=2.0 Hz, H18), 7.29 (1H, dd, J=8.6, 2.0 Hz, H15), 6.86 (1H, d, J=8.6 Hz, H16), 4.44 (2H, s, H13), 3.90 (3H, s, OMe); 13C NMR (75 MHz, CDCl3) delta 156.1, 134.2, 131.5, 129.5, 112.0, 111.9, 56.5, 32.6; EIMS (m/z) calcd for C8H8Br2O [M]+ 277.89, found 278.00.
To a solution of dimethyl sulfoxide (6.50 mL, 91.5 mmol) in CH2Cl2 (45 mL) was added oxalyl chloride (1.57 mL, 18.3 mmol) at -78 °C. The resulting mixture was stirred at the same temperature for 20 min. A solution of 13 (1.99 g, 9.15 mmol) in CH2Cl2 (10 mL) was added to the reaction flask. After stirring for 1 h, triethylamine (6.40 mL, 45.8 mmol) was then added. The reaction mixture was stirred at -78 °C for 1 h, warmed to room temperature, and then stirred for 1 h. The reaction was quenched with 1 N HCl, and the aqueous phase was then separated and extracted with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, and then concentrated in vacuo. Purification by silica gel column chromatography (hexane/EtOAc = 5/1) gave 15 (1.92 g, 8.93 mmol, 98percent) as a colorless powder;
With diisobutylaluminium hydride; In tetrahydrofuran; hexane; at -78 - 0℃; for 1h;Inert atmosphere;
To a solution of methyl 3-bromo-4-methoxybenzoate (12, 2.00 g, 8.16 mmol) in THF (20 mL) was added DIBAL?H (1.00 M in hexane, 20.4 mL) at ?78 °C. The mixture was stirred at ?78 °C for 30 min and 0 °C for 30 min. To the reaction mixture at ?78 °C was added methanol (10 mL) dropwisely followed by saturated aqueous Rochelle salt solution (16 mL) and EtOAc (20 mL). After being stirred at room temperature for 2 h, the aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4, and then concentrated in vacuo. Purification on silica gel column chromatography (hexane/EtOAc=2:1) gave 13 (1.73 g, 7.96 mmol, 98percent) as a colorless solid; Rf 0.17 (hexane/EtOAc=3:1); 1H NMR (300 MHz, CDCl3) delta 7.57 (1H, d, J=2.2 Hz, H18), 7.27 (1H, dd, J=8.6, 2.2 Hz, H15), 6.88 (1H, d, J=8.6 Hz, H16), 4.61 (2H, s, H13), 3.90 (3H, s, OMe); 13C NMR (75 MHz, CDCl3) delta 55.5, 134.6, 132.4, 112.0, 111.8, 64.4, 56.4; EIMS (m/z) calcd for C8H9BrO2 [M]+ 215.98, found 216.05
With palladium diacetate; potassium carbonate; urea; In i-Amyl alcohol; water;Heating;
On the basis of Example 1, the other steps were not changed, and the method of step (2) in Example 1 was changed to 10 gCompound B,<strong>[38493-59-3]3-bromo-4-methoxybenzyl alcohol</strong>,Adding 8.6 g of m-chlorobenzeneboronic acid,18.8 g of potassium carbonate,Urea 82.8 mg,Palladium acetate 210 mg,Isopropyl alcohol / water solvent 100mL,Stir at room temperature. Until the solid completely dissolved, remove the reaction system of oxygen, anaerobic reaction, heating,After completion of the reaction, the isopropanol and part of the water were removed under reduced pressure, and then extracted with ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate, and the palladium salt was removed by suction filtration. , 11.46 g, yield> 95%. The overall yield of this example was 65.5%.
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