PAPER
Arylation of 2-Furyl 4-Fluorophenyl Ketone
3933
4-Fluorophenyl[5-(4-fluorophenyl)furan-2-yl]methanone (5h)
Yield: 84%; white solid; mp 129 °C; Rf = 0.39 (EtOAc–PE, 1:7).
4-[5-(4-Fluorophenyl)(hydroxymethyl)furan-2-yl]-2-hydroxy-
benzoic Acid (3)
A solution of 6 (0.030 mmol) in THF (1 mL) at 60 °C was treated
dropwise with aq 1 M NaOH until TLC analysis indicated a com-
plete consumption of the starting material. The solution was cooled
to 0 °C and diluted with Et2O (5 mL) and aq 1 M NaOH (5 mL). The
organic layer was separated and the aqueous layer was acidified
with concd HCl until pH <1 and finally extracted with EtOAc (5
mL). The organic phase was dried (Na2SO4) and evaporated to give
the desired product (9 mg, 88%) as a white solid;mp 162 °C (dec.).
1H NMR (MeOD): d = 7.83 (d, J1 = 8.76 Hz, 1 H), 7.49 (d, J1 = 8.41
Hz, J1 = 5.45 Hz, 2 H), 7.10 (t, J1 = 8.76 Hz, 2 H), 7.04 (m, 2 H),
6.84 (d, J1 = 3.25 Hz, 1 H), 6.25 (d, J1 = 3.25 Hz, 1 H), 5.82 (s, 1 H).
IR (CHCl3): 1643, 1601 cm–1.
1H NMR (CDCl3): d = 7.98 (dd, J1 = 9.16 Hz, J2 = 5.73 Hz, 2 H),
7.72 (dd, J1 = 8.59 Hz, J2 = 5.73 Hz, 2 H), 7.24 (d, J1 = 4.01 Hz, 1
H), 7.10 (m, 4 H), 6.72 (d, J1 = 4.01 Hz, 1 H).
13C NMR (CDCl3): d = 180.42, 165.96 (JF = 253.29 Hz), 164.23
(JF = 248.17 Hz), 157.45, 151.23, 133.61, 131.74 (JF = 9.22 Hz),
126.99 (JF = 8.07 Hz), 125.56, 116.76, 116.09 (JF = 21.90 Hz),
115.52 (JF = 21.68 Hz), 107.13.
MS (ESI): m/z = 307 [M + Na]+.
Anal. Calcd for C17H10F2O2: C, 71.83; H, 3.55. Found: C, 71.66; H,
3.60.
MS (ESI): m/z = 327 [M – 1]–.
Anal. Calcd for C18H13FO5: C, 65.85; H, 3.99. Found: C, 65.99; H,
3.92.
4-Fluorophenyl(5-phenylfuran-2-yl)methanone (5i)
Yield: 83%; white solid; mp 119 °C; Rf = 0.42 (EtOAc–PE, 1:8).
IR (CHCl3): 1639, 1600 cm–1.
Acknowledgment
1H NMR (CDCl3): d = 8.06 (dd, J1 = 8.71 Hz, J2 = 5.50 Hz, 2 H),
7.78 (d, J1 = 7.33 Hz, 2 H), 7.43 (t, J1 = 7.33 Hz, 2 H), 7.37 (d,
J1 = 7.33 Hz, 1 H), 7.32 (d, J1 = 3.66 Hz, 1 H), 7.18 (dd, J1 = 8.71
Hz, 2 H), 6.82 (d, J1 = 3.66 Hz, 1 H).
This work was supported by the European Union (TRIoH Consorti-
um, LSHB-2003-503480 and THINC, HEALTH-2007-2.3.2-1).
13C NMR (CDCl3): d = 180.35, 165.28 (JF = 251.07 Hz), 158.31,
151.36, 133.65, 131.80 (JF = 8.00 Hz), 129.29, 129.21, 128.88,
125.00, 122.53, 115.50 (JF = 21.72 Hz), 107.45.
References
(1) Summa, V.; Petrocchi, A.; Bonelli, F.; Crescenzi, B.;
Donghi, M.; Ferrara, M.; Fiore, F.; Gardelli, C.;
Gonzalez Paz, O.; Hazuda, D. J.; Jones, P.; Kinzel, O.;
Laufer, R.; Monteaguado, E.; Muraglia, E.; Nizi, E.; Orvieto,
F.; Pace, P.; Pescatore, G.; Scarpelli, R.; Stillmock, K.;
Witmer, M. V.; Rowley, M. J. Med. Chem. 2008, 51, 5843.
(2) (a) Tintori, C.; Corradi, V.; Magnani, M.; Manetti, F.; Botta,
M. J. Chem. Inf. Model. 2008, 8, 2166. (b) Rajamaki, S.;
Innitzer, A.; Falciani, C.; Tintori, C.; Christ, F.; Witvrouw,
M.; Debyser, Z.; Massa, S.; Botta, M. Bioorg. Med. Chem.
Lett. 2009, 19, 3615. (c) Mugnaini, C.; Rajamaki, S.;
Tintori, C.; Corelli, F.; Massa, S.; Witvrouw, M.; Debyser,
Z.; Veljkovic, V.; Botta, M. Bioorg. Med. Chem. Lett. 2007,
17, 5370.
MS (ESI): m/z = 267 [M + H]+, 289 [M + Na]+.
Anal. Calcd for C17H11FO2: C, 76.68; H, 4.16. Found: C, 76.49; H,
4.20.
5-[5-(4-Fluorobenzoyl)furan-2-yl]-1,3-dimethylpyrimidine-
2,4(1H,3H)-dione (5j)
Yield: 51%; pale orange solid; mp 194 °C; Rf = 0.50 (EtOAc–
PE, 1:1).
IR (CHCl3): 1710, 1666 cm–1.
1H NMR (CDCl3): d = 8.00 (s, 1 H), 7.86 (dd, J1 = 8.65 Hz,
J2 = 5.32 Hz, 2 H), 7.21 (d, J1 = 3.99 Hz, 1 H), 7.13 (d, J1 = 3.99 Hz,
1 H), 7.12 (t, J1 = 8.65 Hz, 2 H), 3.49 (s, 3 H), 3.37 (s, 3 H).
13C NMR (CDCl3): d = 180.65, 165.24 (JF = 253.29 Hz), 159.98,
151.79, 150.63, 149.30, 140.20, 133.86, 131.39 (JF = 9.86 Hz),
123.74, 115.61 (JF = 20.02 Hz), 110.86, 104.17, 37.50, 28.12.
(3) Manuscript in preparation.
(4) Data not shown.
(5) (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007,
107, 174–238. (b) Chen, X.; Engle, K. M.; Wang, D.; Yu, J.
Angew. Chem. Int. Ed. 2009, 48, 5094.
MS (ESI): m/z = 351 [M + Na]+.
(6) Liégault, B.; Lapointe, D.; Caron, L.; Vlassova, A.; Fagnou,
Anal. Calcd for C17H13FN2O4: C, 62.19; H, 3.99; N, 8.53. Found: C,
62.01; H, 4.07; N, 8.62.
K. J. Org. Chem. 2009, 74, 1826.
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(8) Dong, J. J.; Roger, J.; Pozgan, F.; Doucet, H. Green Chem.
2009, 11, 1832.
Methyl 4-[5-(4-Fluorophenyl)(hydroxymethyl)furan-2-yl]-2-
hydroxybenzoate (6)
NaBH4 was added portionwise to a solution of 5a (18 mg, 0.053
mmol) in MeOH (1 mL) until TLC indicated a complete consump-
tion of the starting material. The solution was diluted with H2O (10
mL) and EtOAc (10 mL). The organic layer was washed with H2O
(10 mL) and brine (10 mL), dried (Na2SO4), and evaporated. The
residue was purified by flash chromatography (EtOAc–PE, 1:4) to
give the desired product (11 mg, 61%) as a white solid; Rf = 0.27
(EtOAc–PE, 1:4).
1H NMR (CDCl3): d = 10.80 (s, 1 H), 7.81 (d, J1 = 8.42 Hz, 2 H),
7.46 (d, J1 = 8.69 Hz, J2 = 5.33 Hz, 2 H), 7.23 (s, 1 H), 7.14 (d,
J1 = 8.42 Hz, 2 H), 7.08 (d, J1 = 8.69 Hz, 2 H), 6.70 (d, J1 = 3.36 Hz,
1 H), 6.22 (d, J1 = 3.36 Hz, 1 H), 5.87 (s, 1 H), 3.95 (s, 3 H).
(9) McClure, M. S.; Glover, B.; McSorley, E.; Millar, A.;
Osterhout, M. H.; Roschangar, F. Org. Lett. 2001, 3, 1677.
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K. J. Org. Chem. 2009, 74, 1826.
MS (ESI): m/z = 365 [M + Na]+.
(16) Karabelas, K.; Westerlund, C.; Hallberg, A. J. Org. Chem.
Anal. Calcd for C19H15FO5: C, 66.66; H, 4.42. Found: C, 66.81; H,
4.49.
1985, 50, 3896.
Synthesis 2010, No. 22, 3927–3933 © Thieme Stuttgart · New York