Janz and Kaila
JOCNote
The same procedure was followed for all reactions described
in Table 1, except that the reactions were generally run overnight
to account for varying solubilities in THF. Entries 5 and 9 were
purified by trituration with boiling water.
give an orange powder (0.180 g, 76% yield): HPLC purity,
100%; 1H NMR (400 MHz, DMSO-d6) δ 6.68 (d, J = 7.6 Hz,
2 H), 6.73 (t, J = 7.3 Hz, 1 H), 7.14 (dd, J = 8.2, 7.5 Hz, 2 H),
7.41-7.56 (m, 5 H), 7.77 (dd, J = 8.3, 1.3 Hz, 1 H), 7.94-7.98
(m, 1 H), 8.00-8.06 (m, 3 H), 9.33 (s, 1 H); 13C NMR (101 MHz,
DMSO-d6) δ 114.8 (2 CH), 118.4 (CH), 122.7 (CH), 125.4 (C),
125.8 (CH), 126.5 (CH), 127.8 (2 CH), 128.5 (CH), 128.8 (2 CH),
129.3 (CH), 129.6 (2 CH), 129.9 (C), 138.3 (C), 143.2 (C), 143.8
(C), 145.6 (C), 151.2 (C); HRMS (ESIþ) calcd for C21H17N2O
313.13354, found 313.13327.
2-Ethyl-4-vinylquinolin-3-ol (39, Table 3, entry 2). In a 20 mL
Biotage microwave vial (for 5-10 mL reaction volumes),
2-ethyl-3-hydroxyquinoline-4-carboxylic acid (5)22 (0.200 g,
0.921 mmol) was taken up in 3 mL of anhydrous dioxane.
NBS (0.172 g, 0.967 mmol) was added, and the vial was
crimp-sealed and allowed to stir overnight at room temperature.
The vial was then opened, and Pd(PPh3)4 (53 mg, 46 μmol) and
tributyl(vinyl)tin (0.94 mL, 1.0 g, 3.2 mmol) were added before
resealing. The mixture was heated in a microwave reactor for
5 min at 150 °C and then quenched by addition of 2 mL of water
under nitrogen. The vial was then opened, and the contents were
taken up in ethyl acetate, filtered through Celite, evaporated,
and purified by flash chromatography over silica gel (6-50%
ethyl acetate in hexanes) to give a pale yellow solid (89 mg, 48%
yield): HPLC purity, 97.1%; 1H NMR (400 MHz, DMSO-d6) δ
1.28 (t, 3 H), 2.96 (q, J = 7.6 Hz, 2 H), 5.82 (dd, J = 17.8, 1.9 Hz,
1 H), 5.87 (dd, J = 11.7, 1.9 Hz, 1 H), 7.07 (dd, J = 17.9, 11.6
Hz, 1 H), 7.42-7.53 (m, 2 H), 7.82-7.88 (m, 1 H), 7.97-8.02 (m,
1 H), 9.20 (s, 1 H); 13C NMR (101 MHz, DMSO-d6) δ 12.0
(CH3), 26.5 (CH2), 123.5 (CH), 123.5 (dCH2), 124.6 (C), 125.8
(CH), 125.8 (CH), 126.0 (C), 128.7 (CH), 128.9 (CH), 142.3 (C),
145.2 (C), 156.2 (C); HRMS (ESIþ) calcd for C13H14NO
200.10699, found 200.10689.
Representative Procedure: 4-Phenyl-8-(trifluoromethyl)quino-
lin-3-ol (32, Table 2, entry 1). The procedure described above for
the preparation of 2 was followed, using a 10 mL round-
bottomed Biotage microwave vial (for 2-5 mL reaction
volumes) as the reaction vessel and 4 mL of THF as the solvent.
Once complete conversion to 2 had been observed by LC-MS
analysis, phenylboronic acid (0.104 g, 0.856 mmol), Pd(PPh3)2-
Cl2 (27 mg, 39 μmol) and K2CO3 (0.215 g, 1.56 mmol) were
added to the vial, followed by 1 mL of water. The vial was crimp-
sealed and heated in a Biotage Initiator microwave reactor for
5 min at 135 °C. The vial contents were then filtered through
Celite, washing with ethyl acetate, and the ethyl acetate solution
was evaporated and purified by flash chromatography over
silica gel (5-40% ethyl acetate in hexanes), giving a white solid
1
(0.143 g, 63% yield): H NMR (400 MHz, DMSO-d6) δ 7.39
(ddd, J = 6.6, 1.6, 1.4 Hz, 2 H), 7.46-7.52 (m, 1 H), 7.53-7.59
(m, 3 H), 7.68 (d, J = 8.6 Hz, 1 H), 7.95 (d, J = 6.8 Hz, 1 H), 8.89
(s, 1 H), 10.46 (s, 1 H); 13C NMR (101 MHz, DMSO-d6) δ 124.3
(CF3, q, J = 270 Hz), 124.4 (CH-7, q, J = 5.9 Hz), 125.8 (CH),
126.2 (C-8, q, J = 28 Hz), 128.0 (CH), 128.4 (2 CH), 128.5 (C),
128.7 (C), 129.4 (CH), 130.3 (2 CH), 133.0 (C), 138.4 (C), 144.1
(CH), 148.2 (C); HRMS (ESIþ) calcd for C16H11F3NO
290.0787, found 290.0790. Anal. Calcd for C16H10F3NO: C,
66.44; H, 3.48; N, 4.84. Found: C, 66.30; H, 3.34; N 4.64.
The same procedure was followed for all reactions described
in Table 2.
2-Phenyl-4-(phenylamino)quinolin-3-ol (38, Table 3, entry 1).
In a 10 mL round-bottomed microwave vial, 3-hydroxy-2-
phenylquinoline-carboxylic acid (9, see Supporting Informa-
tion; 0.200 g, 0.754 mmol) was taken up in 5 mL THF. NBS
(0.141 g, 0.792 mmol) was added, and the vial was loosely
covered and allowed to stir at room temperature until LC-MS
analysis showed complete consumption of the acid (1.5 h).
Aniline (138 μL, 0.140 g, 1.51 mmol) was then added, and the
vial was crimp-sealed and heated in a microwave reactor for
20 min at 150 °C, until most of the bromide was gone. A large
amount of bright yellow solid precipitated out of solution, and
this was collected by filtration and purified by flash chromato-
graphy over silica gel (1-10% methanol in dichloromethane) to
The same procedure was followed for entry 3, substituting a
1.0 M THF solution of dimethylzinc for the tributyl(vinyl)tin.
Acknowledgment. The authors would like to thank Wyeth
colleagues Dr. Walter Massefski for assistance with NMR
analysis and structure determination and Drs. Thomas
Durand-Reville and John Trzupek for helpful discussions
during the preparation of this manuscript.
Supporting Information Available: Experimental proce-
dures and spectral data for all compounds. This material is
(22) Cross, L. B.; Henze, H. R. J. Am. Chem. Soc. 1939, 61, 2730.
J. Org. Chem. Vol. 74, No. 22, 2009 8877