Reference：
[1] Bulletin de la Societe Scientifique de Bretagne, 1951, vol. 26, p. Sonderheft 5, S. 7, 96[2] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1952, vol. 235, p. 962
2
[ 87-41-2 ]
[ 19477-73-7 ]
Yield
Reaction Conditions
Operation in experiment
66%
at 20℃; for 69 h;
NBS (53.4 g, 300 mmol, 1.5 eq) was added portion wise to a solution of phthalide (Sl-I) (26.83 g, 200 mmol. 1 O eq) in a mixture of TFA (100 mL) and sulfuric acid (45 mL) at rt over 9 h. The reaction mixture (an orange solution) was stirred at rt for about 60 h. (Crude NMR showed the reaction is complete.) Then the reaction mixture was poured onto ice, extracted with methylene chloride (3 x 300 mL). The combined organic phase was dried over MgSO4, filtered and concentrated to afford a yellow solid. The residue was purified by flash-column chromatography (5-10percent ethyl acetate-hexanes) to afford the desired product Sl-2 (white solid, 28.17g, 66percent) and the other regioisomer S3-1 (white solid, 12.7g, 30percent). 1H NMR (400 MHz, CDCl3) 8 8.04 (d, J= 1.8 Hz, 1 H), 7.78 (dd, J= 1.8, 7.9 Hz, 1 H), 7.37 (d, J= 7.9 Hz, 1 H), 5.26 (s, 2 H).
57%
With N-Bromosuccinimide; sulfuric acid; trifluoroacetic acid In ethyl acetate for 95 h;
6-Bromoisobenzofuran-1(3H)-one (20a) In a 100 mL round bottom flask was dissolved isobenzofuran-1(3H)-one (4.01 g, 29.9 mmol) in trifluoroacetic acid (14 mL, 182 mmol) and sulfuric acid (6.5 mL, 122 mmol). N-Bromosuccinimide (7.95 g, 1.49 mmol) was added portionwise over 8 hours and the solution was stirred at room temperature for an additional 87 hours. The solution was diluted with water (40 mL) and ethyl acetate (40 mL). The pH of the aqueous layer was neutralized with 1M aq. NaOH and sat. aq. NaHCO3. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3*50 mL). The combined organic layers were washed with brine (25 mL), dried over Na2SO4, and concentrated on to silica. The crude product was then purified by flash column chromatography using 10-20percent ethyl acetate in hexanes to yield 20a as white solid in 57percent yield. 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J=1.5 Hz, 1H), 7.77 (dd, J=8.3, 1.5 Hz, 1H), 7.40 (d, J=8.3 Hz, 1H), 5.27 (s, 2H). LCMS found 212.9 [M+H]+.
Reference：
[1] Patent: WO2010/132670, 2010, A2, . Location in patent: Page/Page column 50-51
[2] Journal of the American Chemical Society, 2016, vol. 138, # 29, p. 9085 - 9088
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537
[4] Patent: US2015/259331, 2015, A1, . Location in patent: Paragraph 0195
[5] Journal of Heterocyclic Chemistry, 2006, vol. 43, # 5, p. 1195 - 1204
[6] Chemistry of Heterocyclic Compounds, 2010, vol. 46, # 2, p. 140 - 145
[7] Patent: US2011/98311, 2011, A1,
[8] Organic Letters, 2012, vol. 14, # 14, p. 3748 - 3751
[9] Tetrahedron, 2013, vol. 69, # 15, p. 3287 - 3292
[10] Journal of Medicinal Chemistry, 2015, vol. 58, # 9, p. 3997 - 4015
[11] Patent: US2015/231142, 2015, A1,
[12] Patent: CN105153013, 2017, B,
With dihydrogen peroxide; iron(II); In water; at 20℃;pH 2.0;
General procedure: For the Fenton degradation experiment, 10 mL of a Milli Q water sample acidified at pH 2 with 100 muL H2SO4 0.5 mol/L containing 200 ng of each studied anti-inflammatory drug (diclofenac sodium, ibuprofen and ketoprofen) was placed into a 50 mL brown glass bottle. Immediately, 500 muL of Fe2+solution (1 mg/mL Fe2+) and 200 muL of H2O2 (30%) were added into the brown bottle which was kept under magnetic stirring and room temperature for different time intervals in order to perform the degradation process. Because the catalyst (Fe2+) and the oxidant (H2O2) are consumed very fast, these were refreshed at each 30 minutes in the same amounts as it was described previously. To study the Fenton oxidative process efficiency over the selected drugs, different experiments at 30, 60 and 120 minutes were performed. After each Fenton oxidative experiment, the degradation by-products of NAIDs were extracted with organic solvent and analyzed by GC×GC-qMS.
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