Organic Process Research & Development
Article
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7.84 (d, J = 8.9 Hz, 2 H), 7.02 (d, J = 8.9 Hz, 2 H), 6.84 (s, 1
H), 6.61 (s, 1 H), 5.93 (s, 1 H), 4.04 (s, 3 H), 4.03 (s, 3 H),
3.90 (s, 3 H); 13C NMR (CDCl3; 75 MHz): δ 177.0, 162.1,
161.4, 152.1, 151.9, 144.0, 136.6, 127.6, 124.0, 114.4, 112.3,
106.9, 96.2, 62.6, 56.4, 55.5; IR (neat): 3281, 1602, 1498, 1358,
1249, 1182, 1111, 838, 827, 555.
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5,6-Dihydroxy-7-methoxy-2-(4-methoxyphenyl)-chro-
men-4-one (1). To a solution of 6-hydroxy-5,7-dimethoxy-2-
(4-methoxyphenyl)-4H-chromen-4-one (3.91 g, 11.92 mmol, 1
equiv) in MeCN (250 mL) was added MgBr2 etherate (7.69 g,
29.8 mmol, 2.5 equiv). The reaction mixture was stirred for 3 h
at 80 °C. Then a solution of HCl 0.5 M was added, and the
aqueous phase was extracted with EtOAc. The organic phase
was washed three times with HCl 0.5 M, water, and brine. The
separated organic layer was dried over magnesium sulfate and
concentrated under reduced pressure. Recrystallization from
DCM yielded a bright-yellow solid (2.86 g, 9.1 mmol, 76%
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A.; Gentzsch, J.; Grethe, C.; Geuenich,
1
yield). mp 215 °C dec; H NMR (DMSO-d6; 300 MHz): δ
Keppler, O. T.; Ponisch, M.; Bartenschlager, R.; Hernandez, C.;
̈
12.62 (s, 1 H), 8.73 (s, 1 H), 8.07 (d, J = 8.8 Hz, 2 H), 7.13 (d,
J = 8.8 Hz, 2 H), 6.96 (s, 1 H), 6.91 (s, 1 H), 3.94 (s, 3 H), 3.88
(s, 3 H); 13C NMR (DMSO-d6; 75 MHz): δ 182.2, 163.3,
162.2, 154.4, 149.6, 146.2, 129.9, 128.2, 123.0, 114.5, 105.1,
103.1, 91.2, 56.3, 55.5; IR (neat): 3518, 1482, 1464, 1359,
1248, 1179, 1108, 1035, 830, 803, 558; HRMS (ESI+): 315.09
[M + H]+
Lemasson, M.; Rosenberg, A.; Wong-Staal, F.; Davioud-Charvet, E.;
Pietschmann, T. Gastroenterolgy 2012, 143, 213−222.
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2197−2217.
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Y.; Seron, K. Viruses 2012, 4,
ASSOCIATED CONTENT
* Supporting Information
(16) Xia, J. F.; Gao, J. J.; Inagaki, Y.; Kokudo, N.; Nakata, M.; Tang,
W. Drug Discovery Ther. 2013, 7, 1−8.
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S
(17) Kavala, V.; Lin, C.; Kuo, C.-W.; Fang, H.; Yao, C.-F. Tetrahedron
2012, 68, 1312−1329.
Purification protocol for acetylated acetophenone 12 and
acetophenone 3 applied in the screen of reaction conditions
1
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(Table 1), H and 13C NMR spectra for compounds 1, 3, 4, 6,
10, and 12. This material is available free of charge via the
AUTHOR INFORMATION
Corresponding Author
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(22) Black, T. H.; McDermott, T. S.; Brown, G. A. Tetrahedron Lett.
1991, 32, 6501−6502.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Michel Schmitt is acknowledged for NMR spectra acquisition.
This study was supported by the Centre National de la
Recherche Scientifique (CNRS, France, UMR 7509) and by the
Laboratoire d’Excellence (LabEx) ParaFrap (Grant LabEx
ParaFrap ANR-11-LABX-0024. X.M.B. thanks the French
Ministry of Research and Education for granting him a Ph.D.
(MRT) fellowship.
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dx.doi.org/10.1021/op4003642 | Org. Process Res. Dev. XXXX, XXX, XXX−XXX