10.1002/cbdv.201800334
Chemistry & Biodiversity
HELVETICA
From 1.0 g (5.1 mmol) of 4-fluoro-3-ethoxycarbonyl benzofuran, 1.4 g (56.5 mmol) of magnesium powder, and 0.13 g (0.51 mmol) of iodine at
room temperature. Yield: 82%. 1H-NMR (CDCl3, 300 MHz): 7.10 (d, J=9, 1 H, Ph); 6.98 (t, J=9, 1 H, Ph); 6.87-6.71 (m, 1 H, Ph); 4.93 (dd, J=9, 7, 1
H, CH2); 4.68 (t, J=9, 1 H, CH); 4.32 (dd, J=9, 7, 1 H, CH2); 3.78 (s, 3 H, OCH3).
General Procedure for the Preparation of 7-Benzoyl-2,3-dihydro-3-methoxycarbonyl benzofuran Using Microwave Reactor
In a typical experiment, 0.04 – 0.06 mmol (0.1 equiv) of Bi(OTf)3 was placed into a 10 mL pressurized microwave reaction vessel. Then, 0.8 -1.2
mmol (2.0 equiv) of benzoyl chloride was charged to the reaction vessel and was allowed to stir. 0.4 – 0.6 mmol (1.0 equiv) of dihydro
benzofuran was added to the reaction vessel using 1.5 mL of nitrobenzene, quickly followed by flushing the reaction vessel with N2 and sealed
with a high-pressure Teflon cap. The reaction vessel was placed in the microwave and allowed to react for the allotted reaction time at the
reported temperature. All microwave reactions were performed with high stirring, 40 PSI and at 250-watt power. The reaction was quenched
with 10 mL of water and extracted with CH2Cl2. The organic layer was washed with concentrated NaHCO3 solution and brine. Nitrobenzene was
removed by running the product through a thick pad of silica with hexane, causing the product to get stuck in the silica, followed by flushing
the silica with CH2Cl2 to retrieve the product. The products were isolated by flash chromatography (5 – 20% CH2Cl2 in hexane).
7-Benzoyl-5-chloro-2,3-dihydro-3-methoxycarbonyl benzofuran [1] (4a)
From 0.10 g (0.47 mmol) of 5-chloro-2,3-dihydro-3-methoxycarbonyl benzofuran, 0.13 g (0.94 mmol) of benzoyl chloride, and 0.03 g (0.047
mmol) of bismuth(III) trifluoromethanesulfonate. Yield: 77%. 1H-NMR (CDCl3, 500 MHz): 7.82 (d, J=5, 2 H, Ph); 7.63-7.60 (m, 1 H, Ph); 7.53 (s, 1 H,
Ph); 7.48 (t, J=10, 2 H, Ph); 7.44 (s, 1 H, Ph); 4.99 (dd, J=10, 5, 1 H, OCH); 4.76 (t, J=10, 1 H, CH); 4.40 (dd, 10, 5, 1 H, OCH); 3.84 (s, 3 H, OCH3).
HR-MS: 317.0571 ([M + H] +, C17H13O4Cl; calc. 317.0575).
7-Benzoyl-5-methyl-2,3-dihydro-3-methoxycarbonyl benzofuran [1] (4b)
From 0.10 g (0.52 mmol) of 5-methyl-2,3-dihydro-3-methoxycarbonyl benzofuran, 0.15 g (1.04 mmol) of benzoyl chloride, and 0.03 g (0.052
mmol) of bismuth(III) trifluoromethanesulfonate. Yield: 80%. 1H-NMR (CDCl3, 300 MHz): 7.81 (d, J=6, 2 H, Ph); 7.56 (t, J=6, 1 H, Ph); 7.45 (t, J=9,
2 H, Ph); 7.38 (s, 1 H, Ph); 7.25 (s, 1 H, Ph); 4.91 (dd, J=9, 7, 1 H, OCH); 4.69 (t, J=9, 1 H, CH); 4.34 (dd, J=9, 7, 1 H, OCH); 3.81 (s, 3 H, OCH3); 2.33 (s,
3 H, Ph-CH3). 13C-NMR (CDCl3, 125 MHz): 20.66; 46.59; 52.74; 73.38; 121.18; 126.05; 128.26; 129.80; 129.90; 130.04; 131.0; 132.70; 137.86; 156.70;
121.28; 194.44. HR-MS: 296.1040 ([M]+, C18H16O4; calc. 296.1043).
7-Benzoyl-5-fluoro-2,3-dihydro-3-methoxycarbonyl benzofuran [1] (4c)
From 0.10 g (0.51 mmol) of 5-fluoro-2,3-dihydro-3-methoxycarbonyl benzofuran, 0.14 g (1.02 mmol) of benzoyl chloride, and 0.033 g (0.050
mmol) of bismuth(III) trifluoromethanesulfonate. Yield: 51%. 1H-NMR (CDCl3, 500 MHz): 7.82 (d, J=10, 2 H, Ph); 7.61 (t, J=7, 2 H, Ph); 7.49 (t,
J=15, 2 H, Ph); 7.45 (s, 1 H, Ph); 4.97 (dd, J=10, 5, 1 H, OCH), 4.75 (t, J=10, 1 H, CH); 4.44 (dd, J=10, 5, 1 H, OCH); 3.86 (s, 3 H, OCH3).
5-Chloro-7-(4-chlorobenzoyl)-2,3-dihydro-3-methoxycarbonyl benzofuran (4d)
From 0.10 g (0.47 mmol) of 5-chloro-2,3-dihydro-3-methoxycarbonyl benzofuran, 0.17 g (0.94 mmol) of 4-chlorobenzoyl chloride and 0.06 g
(0.092 mmol) of bismuth(III) trifluoromethanesulfonate. Yield : 70 %. 1H-NMR (CDCl3, 300 MHz): 7.77 (d, J=9, 2 H, Ph); 7.55 (s, 1 H, Ph); 7.47-
7.44 (m, 3 H, Ph); 4.98 (dd, J=9, 6, 1 H, OCH); 4.74 (t, J=9, 1 H, CH); 4.39 (dd, J=9, 6, 1 H, OCH); 3.85 (s, 3 H, OCH3).
5-Chloro-7-(4-(trifluoromethyl)benzoyl)-2,3-dihydro-3-methoxycarbonyl benzofuran- (4e)
From 0.10 g (0.47 mmol) of 5-chloro-2,3-dihydro-3-methoxycarbonyl benzofuran, 0.20 g (0.94 mmol) of 4-(trifluromethyl)benzoyl chloride and
0.06 g (0.092 mmol) of bismuth(III) trifluoromethanesulfonate. Yield : 79 %. 1H-NMR (CDCl3, 500 MHz): 8.02 (d, J=5, 1H, Ph); 7.91 (d, J=5, 1H,
Ph); 7.80-7.75 (m, 2 H, Ph); 7.48-7.33 (m, 2 H, Ph); 4.99 (dd, J=10, 5, 1 H, OCH); 4.76 (dd, J=10, 5, 1 H, CH); 4.45 (dd, J=10, 5, 1 H, OCH). HR-MS:
371.0290 ([M + H]+, C17H10O4F3Cl; calc. 371.0292).
5-Chloro-7-(4-fluorobenzoyl)-2,3-dihydro-3-methoxycarbonyl benzofuran (4f)
8
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