* 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.
Intermediate 3 (5.1 kg, 24.3 mol), acetic anhydride (10 L), and sodium acetate(3.0 kg, 36.6 mol) were added to a 50-L reactor. The mixture was heated understirring at 110–130 C (large amount of gas evolution) and kept at 130 C for 2 h.After being cooled to 60 C, ethanol (10 Lto consume the acetic anhydride) wasadded portion-wise and the mixture was stirred at 60–80 C for 2 h. It was thencooled to rt andwater (10 L) and ethyl acetate (10 L) were added. The organic phasewas separated, washed with 2 N NaOH and water, and dried over sodium sulfate.The solvent was removed by distillation to afford a colorless liquid 4 (2.98 kg, 83 percentyield, or 77 percent combined yield from 2, 99.6 percent purity). 1H-NMR (CDCl3, ppm): d7.55–7.56 (d, 1H), 7.47–7.49 (d, 1H), 7.07 (s, 1H), 6.90–6.92 (dd, 1H), 6.71–6.72 (d,1H), 3.88 (s, 3H) [27].
Reference:
[1] Research on Chemical Intermediates, 2016, vol. 42, # 5, p. 4433 - 4442
2
[ 15832-09-4 ]
[ 50551-63-8 ]
Reference:
[1] Organic and Biomolecular Chemistry, 2008, vol. 6, # 19, p. 3486 - 3496
3
[ 13196-11-7 ]
[ 74-88-4 ]
[ 50551-63-8 ]
Reference:
[1] Chemical and Pharmaceutical Bulletin, 2013, vol. 61, # 10, p. 997 - 1001
4
[ 50551-61-6 ]
[ 50551-63-8 ]
Reference:
[1] Patent: WO2018/140513, 2018, A1, . Location in patent: Page/Page column 102
[2] Journal of the American Chemical Society, 1951, vol. 73, p. 872
5
[ 673-22-3 ]
[ 50551-63-8 ]
Reference:
[1] Synlett, 2006, # 4, p. 567 - 570
[2] Journal of the American Chemical Society, 1951, vol. 73, p. 872
[3] Research on Chemical Intermediates, 2016, vol. 42, # 5, p. 4433 - 4442
[4] Research on Chemical Intermediates, 2016, vol. 42, # 5, p. 4433 - 4442
[5] Patent: WO2018/140513, 2018, A1,
6
[ 108639-46-9 ]
[ 50551-63-8 ]
Reference:
[1] European Journal of Organic Chemistry, 2018, vol. 2018, # 22, p. 2774 - 2779
[2] Justus Liebigs Annalen der Chemie, 1900, vol. 312, p. 332
[3] Organic Letters, 2016, vol. 18, # 21, p. 5624 - 5627
7
[ 150-19-6 ]
[ 50551-63-8 ]
Reference:
[1] Justus Liebigs Annalen der Chemie, 1900, vol. 312, p. 332
[2] Organic Letters, 2016, vol. 18, # 21, p. 5624 - 5627
[3] European Journal of Organic Chemistry, 2018, vol. 2018, # 22, p. 2774 - 2779
With sodium dodecanethiolate; In N,N-dimethyl-formamide; at 130℃; for 3h;Large scale;
DMF (18 L), sodium dodecanethiolate (7.6 kg, 33.9 mol), and 4 (2.95 kg, 19.9 mol)were added to a 50-L reactor. The reaction mixture was heated and stirred at 130 Cfor 3 h, then cooled to rt, and 4 N NaOH was added to adjust the pH to 13. Thesolution was extracted with petroleum ether three times. The aqueous phase was acidified with 2 N HCl to pH 2 and extracted with ethyl acetate three times. Theethyl acetate phases were combined, washed with water, and dried over sodiumsulfate. The solvent was removed under vacuum and the residue was left overnightat room temperature to afford 1 as a light brown solid (2.65 kg, 90 percent yield, 99.5 percentpurity), m.p. 54?56 C. 1H-NMR (CDCl3, ppm): d 7.55 (s, 1H), 7.44?7.46 (d, 1H),7.03 (s, 1H), 6.81?6.83 (d, 1H), 6.72 (s, 1H), 5.09 (br, 1H).
With hydrogenchloride; lithium iodide; In 2,3,5-trimethyl-pyridine;
Reference Example 207 To a solution of 6-methoxybenzofuran (16.9 g) in collidine (200 ml) was added lithium iodide (30.5 g), and the mixture was refluxed under argon atmosphere for 1 day and cooled. To the mixture was added 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with 2N hydrochloric acid (5 times) and then washed with water and saturated brine, and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography to give dark brown oil of 6-hydroxybenzofuran (2.9 g). 1H-NMR (200 MHz, CDCl3) delta 8 5.04 (s, 1H), 6.69 (dd, 1H, J=2.6, 1.0 Hz), 6.79 (dd, 1H, J=8.4, 2.2 Hz), 7.00 (d, 1H, J=2.0 Hz), 7.42 (d, 1H, J=8.4 Hz), 7.52 (d, 1H, J=2.2 Hz).
Reference Example 206 A suspension of 6-methoxybenzofuran-2-carboxylic acid (22.2 g) and copper powder (3.7 g) in quinoline (200 ml) was refluxed under nitrogen atmosphere for 2 hours and cooled, and to the suspension was added 2N hydrochloric acid. The mixture was extracted with ethyl acetate, and the organic layer was washed with 2N hydrochloric acid (6 times) and then washed with water and saturated brine, and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated to give dark brown oil of 6-methoxybenzofuran (17.1 g). 1H-NMR (200 MHz, CDCl3) delta 3.86 (s, 3H), 6.69 (dd, 1H, J=2.2, 1.2 Hz), 6.88 (dd, 1H, J=8.4, 2.2 Hz), 7.04 (br, 1H), 7.45 (d, 1H, J=6.6 Hz), 7.53 (d, 1H, J=1.4 Hz).
Preparation of 2-(<strong>[50551-63-8]6-methoxy-1-benzofuran</strong>-2-yl)-4(3H)-quinazolinone (example of general procedure); n-BuLi (6.0 mL, 2.5 M, 15 mmol) was added dropwise to a solution of <strong>[50551-63-8]6-methoxy-1-benzofuran</strong> (2.002 g, 13.5 mmol) [M. Hideku etal., PCT Int. Appl. (2002) WO 2002100850] inTHF (30 mL) at -78C over 5 min. The solution was stirred at -78C for 5 min. then triisopropylborate (15 mL, 65 mmol) was added and the mixture was warmed to room temperature. The mixture was quenched with HCI (2 M, 60 mL) and the organic solvent was removed in vacuo. Water (80 mL) and salt (10 g) were added and the mixture was cooled to 0C to give a white precipitate which was washed with water and hexanes to give <strong>[50551-63-8]6-methoxy-1-benzofuran</strong>-2-ylboronic acid (1.408 g, 13.5 mmol). 1H NMR (DMSO-de) 8 ppm 8.37 (s, 2H), 7.53 (d, 1H, J=8.6 Hz), 7.37 (d, 1H, J=0.9 Hz), 7.12 (bd, 1H, J=1.7 Hz), 6.86 (dd, J=8.6, 2.2 Hz), 3.81 (s, 3H).
Benzen-1,3-diolwas treated with chloroacetonitrile in the presence of HClto give 6-hydroxy-coumaran-3-one. This compound was reducedwith NaBH4 and dehydrated by acid to give <strong>[13196-11-7]6-hydroxybenzofuran</strong>.Compound 1017) was obtained by methylation ofalcohol described as compound 4. Compound 10 was obtainedby methylation of alcohol described as compound 4. Colorlessoil, 1H-NMR (500 MHz, CDCl3) delta: 3.72 (3H, s), 6.58 (1H, d,J=1.7 Hz), 6.77 (1H, dd, J=2.3, 8.6 Hz), 6.94 (1H, d, J=2.3 Hz),7.34 (1H, d, J=8.6 Hz), 7.43 (1H, d, J=1.7 Hz). 13C-NMR(125 MHz, CDCl3) delta: 55.7, 96.0, 106.5, 112.1, 120.8, 121.3,144.2, 156.1, 158.2. Its spectral data are in accordance withpreviously reported data.
With tin-exchanged H-b zeolite (Sn-b); for 0.5h;Reflux;
General procedure: A 25 mL round-bottomed flask was charged with 2-aryloxyacetaldehyde diethyl acetals (1 mmol), Sn-b (0.1 g), andtrifluorotoluene (10 mL). The mixture was stirred under refluxingcondition and monitored by GC. Upon completion, the mixture wascooled to room temperature, and the catalyst Sn-b was filtrate off.The filter cake was washed with trifluorotoluene (10 mL3). Thecombined filtratewas concentrated under vacuum. The residuewaspurified by flash column chromatography on SiO2 (petroleumether/ethyl acetate) to afford the desired 2,3-unsubstituted benzo[b]furans.
With sodium acetate; acetic anhydride; at 110 - 130℃;Large scale;
Intermediate 3 (5.1 kg, 24.3 mol), acetic anhydride (10 L), and sodium acetate(3.0 kg, 36.6 mol) were added to a 50-L reactor. The mixture was heated understirring at 110-130 C (large amount of gas evolution) and kept at 130 C for 2 h.After being cooled to 60 C, ethanol (10 Lto consume the acetic anhydride) wasadded portion-wise and the mixture was stirred at 60-80 C for 2 h. It was thencooled to rt andwater (10 L) and ethyl acetate (10 L) were added. The organic phasewas separated, washed with 2 N NaOH and water, and dried over sodium sulfate.The solvent was removed by distillation to afford a colorless liquid 4 (2.98 kg, 83 %yield, or 77 % combined yield from 2, 99.6 % purity). 1H-NMR (CDCl3, ppm): d7.55-7.56 (d, 1H), 7.47-7.49 (d, 1H), 7.07 (s, 1H), 6.90-6.92 (dd, 1H), 6.71-6.72 (d,1H), 3.88 (s, 3H) [27].
With copper(l) iodide; di-tert-butyl peroxide; XPhos; at 120℃; for 24h;Inert atmosphere; Sealed tube; Schlenk technique;
General procedure: To a reaction tube were added 20 mol % CuI, 20 mol % KI (or Xphos), 0.25 mmol heterocycles, 3.0 equiv DTBP, and 1.5 mL cyclic ethers under a nitrogen atmosphere. The resulting mixture was heated at 120 C. After 24 h, the solvent was removed under vacuum, and the residue was purified by flash chromatography (SiO2, petroleum ether/ethyl acetate10:1).