1804
G. Martinez-Ariza et al.
LETTER
was stirred for 2 h at r.t. and excess TFAA was removed in
vacuo by means of azeotroping with toluene (5 × 10 mL) to
give 1.32 g (93% yield) of a yellow solid product. 1H NMR
(400 MHz, CDCl3): δ = 8.42 (t, J = 1.8 Hz, 1 H), 8.37–8.34
(m, 1 H), 7.63 (ddd, J = 8.1, 2.1, 1.0 Hz, 1 H), 7.49 (t, J = 8.0
Hz, 1 H), 6.28 (q, J = 4.0 Hz, 1 H). 13C NMR (100 MHz,
CDCl3): δ = 162.2, 159.8, 135.4, 134.0, 130.6, 130.4, 129.7,
128.9, 128.7, 127.2, 125.4, 121.6, 118.8, 92.4 (q, JC–F = 35.5
Hz). MS: m/z = 264 [M + H]+.
CDCl3): δ = 176.0, 166.9, 163.0 (d, JC–F = 281.9 Hz), 133.3,
130.6 (d, JC–F = 9.2 Hz), 129.0, 128.8, 128.2 (d, JC–F = 8.6
Hz), 126.8, 121.9, 116.2 (d, JC–F= 22.3 Hz), 115.9 (d, JC–F
=
22.2 Hz), 68.1. MS: m/z = 256 [M + H]+.
(18) (a) Dubernet, M.; Caubet, V.; Guillard, J.; Viaud-Massuard,
M. C. Tetrahedron 2005, 61, 4585. (b) Choi, D. S.; Huang,
S.; Huang, M.; Barnard, T. S.; Adams, R. D.; Seminario, J.
M.; Tour, J. M. J. Org. Chem. 1998, 63, 2646. (c) Xie, J.;
Lown, J. W. Tetrahedron Lett. 1994, 35, 5555.
(16) (a) Becker, D. P.; DeCrescenzo, G.; Freskos, J.; Getman, D.
P.; Hockerman, S. L.; Li, M.; Mehta, P.; Munie, G. E.;
Swearingen, C. Bioorg. Med. Chem. Lett. 2011, 11, 2723.
(b) Kahlon, D. K.; Lansdell, T. A.; Fisk, J. S.; Hupp, C. D.;
Friebe, T. L.; Hovde, S.; Jones, A. D.; Dyer, R. D.; William
Henry, R.; Tepe, J. J. J. Med. Chem. 2009, 52, 1302.
(c) Obrecht, D.; Spiegler, C.; Schönholzer, P.; Müller, K.;
Heimgartner, H.; Stierli, F. Helv. Chim. Acta 1992, 75, 1666.
(17) General Procedure for the Preparation of Compounds 1
(Route B), Exemplified for Compound 1d
(19) General Procedure for the Preparation of Compounds 2,
Exemplified for Compound 2c
3-Bromomaleic anhydride (1.0 equiv, 5.65 mmol, 1.0 g) was
dissolved in AcOH (20 mL). Methylamine hydrochloride
(1.0 equiv, 5.65 mmol, 0.37 g) was then added, and the
reaction was heated at 80 °C for 3 h. Solvent was removed in
vacuo, and the crude mixture was purified by column
chromatography over silica gel (EtOAc–hexane 0–30%)
using an ISCOTM purification system to afford 0.97 g of a
white solid (90% yield). 1H NMR (400 MHz, CDCl3): δ =
6.89 (s,1 H), 3.08 (s,3 H). 13C NMR (100 MHz, CDCl3): δ =
168.5, 165.3, 131.9, 131.3, 24.6. MS: m/z = 191 [M + H]+.
(20) General Procedure for the Preparation of Compounds 5,
Exemplified for Compound 5a
Phenylglycine (1.0 equiv, 6.60 mmol, 1.0 g) was added to
2.0 M NaOH (20 mL) in a 100 mL round-bottomed flask.
The solution was cooled to 0 °C in an ice bath, and then 4-
fluorobenzoylchloride (9, 1.0 equiv, 6.60 mmol, 0.78 mL)
was added dropwise over 20 min. The reaction was allowed
to warm to r.t. and stirred for 2 h. The solution was then
made slightly acidic (pH 5–6) by dropwise addition of 2.0 M
HCl and was extracted with EtOAc (5 × 75 mL). The organic
phase was dried over MgSO4 and concentrated in vacuo to
yield 8d as white solid (1.6 g). 1H NMR (400 MHz, DMSO-
d6): δ = 12.96 (s, 1 H), 9.06 (d, J = 7.4 Hz, 1 H), 7.99 (dd,
J = 8.4, 6.0 Hz, 2 H), 7.50–7.46 (m, 2 H), 7.39–7.24 (m, 4
H), 5.58 (d, J = 7.4 Hz, 1 H). 13C NMR (100 MHz, DMSO-
d6): δ = 172.3, 166.8, 166.6, 165.7, 163.7 (d, JC–F = 87.9 Hz),
137.4, 132.5 (d, JC–F = 12.4 Hz), 130.9 (d, JC–F = 10.1 Hz),
130.6, 128.8, 128.6, 128.4, 127.8, 116.0 (d, JC–F = 21.9 Hz),
115.5 (d, JC–F = 21.8 Hz), 57.4. MS: m/z = 274 [M + H]+.
Compound 8d (5.86 mmol, 1.6 g) was then added to Ac2O (3
mL) in a 25 mL round-bottomed flask. The mixture was
stirred for 2 h at r.t. and excess Ac2O was removed in vacuo
via azeotroping with toluene (5 × 10 mL) to give 1.36 g of a
yellow solid product (81% yield over two steps). 1H NMR
(400 MHz, CDCl3): δ = 8.15–8.07 (m, 2 H), 7.50–7.35 (m, 5
H), 7.28–7.13 (m, 2 H), 5.51 (s, 1 H). 13C NMR (100 MHz,
4-Phenyl-2-(trifluoromethyl)oxazol-5(4H)-one (1a, 1.0
equiv, 1,3 mmol, 0.30 g) and 3-bromo-phenyl-1H-pyrrole-
2,5-dione (2a, 1.0 equiv, 1,3 mmol, 0.33 g) were dissolved
in toluene (20 mL). DIPEA (2.0 equiv, 2.6 mmol, 0.45 mL)
was added. The reaction mixture was stirred at r.t. for 15
min. Solvent was evaporated in vacuo, and the crude
material was purified by column chromatography over silica
gel (EtOAc–Hexane 0–50%) using an ISCOTM purification
system to afford 0.44 g of a yellow solid (91% yield).
Crystals suitable for X-ray diffraction studies were obtained
by recrystallization of the pure product from CH2Cl2 and
hexane. 1H NMR (400 MHz, CDCl3): δ = 7.41 (m, 10 H),
8.44 (s, 1 H). 13C NMR (100 MHZ, CDCl3): δ = 166.4,
162.0, 134.6, 133.4, 132.8, 131.9, 130.3, 129.6, 129.2,
129.1, 128.5, 126.9, 125.9, 121.9, 119.0, 29.6 (m). MS:
m/z = 357 [M + H]+.
(21) Complete crystallographic information for compound 5a can
be found in: Roberts, S. A.; Martinez-Ariza, G.; Dietrich, J.;
Hulme, C. Acta Crystallogr., Sect. E: Struct. Rep. Online
2012, 68, 496.
Synlett 2013, 24, 1801–1804
© Georg Thieme Verlag Stuttgart · New York