R
SYNTHETIC COMMUNICATIONSV
11
heated in acetic anhydride (8 mL) at 55 ꢀC for 30 min. Then, 2-(nitromethylene) thiazo-
lidine 4 (1.00 mmol, 146 mg) was added to the reaction mixture and refluxed overnight
at 90 ꢀC. After cooling the reaction mixture to room temperature, the solvent was
removed under the reduced pressure and the crude residue was purified by flash col-
umn chromatography (silica gel, EtOAc/n-hexane; 1:7) to give 5 as yellow solid. Yieꢁld1:
48%; mp 98–100 ꢀC. IR (KBr): ꢀ ¼ 2958, 1745, 1647, 1508, 1358, 1217, 1082, 839 cm
.
1 H NMR (400 MHz, CDCl3): d 7.27 (d, J ¼ 8.1 Hz, 2H), 7.13–7.10 (m, 2H), 7.01 (d,
J ¼ 7.9 Hz, 2H), 6.90 (t, J ¼ 8.7 Hz, 2H), 3.31 (s, 3H), 2.30 (s, 3H), 1.98 (d, J ¼ 4.8 Hz,
6H). 13 C NMR (100 MHz, CDCl3): d 171.6, 168.6, 162.0 (d, C-F carbon, J ¼ 247.0 Hz),
144.7, 140.4, 132.6 (d, b-C to C-F, Jmeta= 18.0 Hz), 131.2, 129.4, 129.3, 128.4, 127.5,
115.2 (d, a-C to C-F, Jortho= 22.0 Hz), 37.2, 21.4, 20.9, 17.3. LC-MS (ESþ) m/z (%):
342.2 [M þ H]þ. HRMS: m/z (ESI-TOF, [M þ H]þ) calcd for C20H20FNO3: 342.1505.
Found: 342.1500.
Route B
4-Chlorobenzoic acid 7e: 2-(4-Chloro-N-methylbenzamido)-2-(4-fluorophenyl)acetic acid
3e (0.715 mmol, 230 mg) in acetic anhydride (2.23 mL) was irradiated at 0–150 W for
15 min in closed glass vial in a CEM Discover microwave reactor at 55 ꢀC. Then, 2-
(nitromethylene)thiazolidine 4 (0.255 mmol, 38 mg) was added the reaction mixture and
irradiated at 0-150 W for further 45 min at 80 ꢀC. After cooling the reaction mixture to
room temperature, the solvent was removed under the reduced pressure and the residue
was purified by flash column chromatography (silica gel, EtOAc/n-hexane;1:18) to
give 7e.
4-Fluoro-N-methyl-N-(4-nitrobenzoyl)benzamide 6d (route a): Yellow solid. Yield:
34%; mp 131-133 ꢀC. IR (KBr): ꢀ ¼ 3117, 1701, 1651, 1600, 1519, 1342, 1288, 1041,
852 cmꢁ1
.
1 H NMR (400 MHz, CDCl3): d 8.10 (d, J ¼ 8.0 Hz, 2H), 7.62-7.56 (m, 4H),
7.00 (t, J ¼ 8.0 Hz, 2H), 3.50 (s, 3H). 13 C NMR (100 MHz, CDCl3): d 172.9, 171.9,
165.3 (d, C-F carbon, J ¼ 154.0 Hz), 149.2, 141.6, 131.7 (d, b-C to C-F, Jmeta= 9.0 Hz),
131.1, 129.3, 123.7, 116.2 (d, a-C to C-F, Jortho= 22.0 Hz), 34.6. LC-MS (ESþ) m/z (%):
297 [M-4H]þ. Calculated for C15H11FN2O4; 302.0703; C, 59.61; H, 3.67; N, 9.27. Found:
C, 59.84; H, 3.84; N, 9.22.
4-Chlorobenzoic acid 7e (route a and route B): White solid. Yield: 83%; mp 235-
237 ꢀC (lit.[38,39] mp 236-237 ꢀC). IR (KBr): ꢀ ¼ 3093, 1685, 1593, 1423, 1280, 1176,
1091, 759 cmꢁ1
.
1 H NMR (400 MHz, DMSO-d6): d 13.1 (s, 1H), 7.90 (dd, J ¼ 8.0,
4.0 Hz, 2H), 7.53 (d, J ¼ 8.0, 4.0 Hz, 2H). 13 C NMR (100 MHz, DMSO-d6): d 169.9,
138.3, 131.7, 130.2, 129.3. LC-MS (ES-) m/z (%): 155 [M-H]-.
General procedure
Synthesis of 4-substituted-N-isopropyl-N-(isopropylcarbamoyl)benzamides 9a-f
and 4-substituted-N-cyclohexyl-N-(cyclohexylcarbamoyl)benzamides 11a-g
2-(4-Chloro-N-methylbenzamido)-2-(4-fluorophenyl) acetic acid 3e (0.47 mmol, 151 mg)
was dissolved in acetonitrile (10 mL) and DIPC (diisopropyl carbodiimide) 8 (0.3 mL)
was added. Then, the reaction mixture was heated at 55 ꢀC for 30 min. Then, DIPA