Page 11 of 15
The Journal of Organic Chemistry
51.5, 47.1. HRMS Calcd for C11H16NO [M+H] 178.1232.
to room temperature, the reaction mixture was transferred to a
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separatory funnel, followed by the addition of saturated NH4Cl
solution (2 mL). The mixture was extracted with ethyl acetate
three times (3 x 10 mL). The combined organic layer was dried
over anhydrous MgSO4. After rotatory evaporation to remove
the solvents, the product was purified using column
chromatography (0 – 100% ethyl acetate: hexanes).Yellow
Found: 178.1225.
3,3-dimethyl-1-(pyridin-3-yl)butan-2-one (11b). Synthesized
from 3,3-dimethyl-2-butanone (0.55 mmol, 1.1 equiv, 55.1 mg,
68.8 µL), and 3-iodopyridine (0.5 mmol, 1 equiv, 102.5 mg)
according to the general procedure described above. Yellow oil.
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Yield, 95.8 mg, 54.1%. H NMR (CDCl3, 500 MHz, ppm): δ
solid. Yield, 91.0 mg, 39.3%. H NMR (CDCl3, 500 MHz,
8.45 (1H, d, J = 1.4 Hz), 8.37 (1H, s), 7.49 (1H, t, J = 7.3 Hz),
7.21 (1H, t, J = 7.8 Hz), 3.77 (2H, s), 1.21 (9H, s). 13C{1H}
NMR (CDCl3, 125 MHz, ppm): δ211.9, 150.6, 148.2, 137.4,
130.7, 123.3, 44.7, 40.2, 26.4. HRMS Calcd for C11H16NO
[M+H] 178.1232. Found: 178.1238.
ppm): δ 8.49-8.48 (2H, m), 7.92 (2 H, d, J = 8.7 Hz), 7.55 (1H,
d, J = 7.8 Hz), 7.42 (2H, d, J = 8.3 Hz), 7.24 (1H, d, J = 7.8 Hz),
4.24 (2H, s). 13C{1H} NMR (CDCl3, 125 MHz, ppm): δ 195.3,
150.7, 148.6, 140.1, 137.3, 134.6, 129.9, 129.2, 128.7, 123.6,
42.4. HRMS Calcd for C13H11NOCl [M+H] 232.0529. Found:
232.0536.
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2-(pyridin-3-yl)cyclohexanone (12b).44 Synthesized from
cyclohexan-1-one (1.1 mmol, 1.1 equiv, 105.7 mg, 106.5 µL),
and 3-bromopyridine (1.0 mmol, 1 equiv, 158.0 mg, 96.4 µL)
according to the general procedure described above. Yellow oil.
Yield, 111.8 mg, 63.8%. 1H NMR (CDCl3, 500 MHz, ppm): δ
8.49 (1H, d, J = 5.0 Hz), 8.37 (1H,s), 7.48 (1H, d, J = 6.0 Hz),
7.26 (1H, dd, J = 7.7, 3.2 Hz), 3.62 (1H, dd, J = 17.9, 5.5 Hz),
2.56-2.48 (2H, m), 2.30-2.26 (1H, m), 2.20-2.26 (1H, m), 2.20-
2.14 (1H, m), 1.02-1.78 (4H, m). 13C{1H} NMR (CDCl3, 125
MHz, ppm): δ 209.3, 150.1, 148.4, 136.3, 134.4, 123.3, 55.0,
42.3, 35.5, 27.9, 25.5. HRMS Calcd for C11H14NO [M+H]
176.1075. Found: 176.1082.
1-(4-bromophenyl)-2-(pyridin-3-yl)ethanone (8b). To an
oven-dried microwave reaction vial (standard Wheaton® glass
vials, Item# 224882) containing a stirring bar was charged with
Pd2(dba)3 (9.2 mg, 0.01 mmol, 1 mol %) and XPhos (4.8 mg,
0.01 mmol, 1 mol %) and toluene (2.0 ml). The catalyst and
ligand were premixed at r.t. for 30 minutes under Ar. Then
NaOtBu (230.6 mg, 2.40 mmol, 2.4 equiv.) and 4’-
bromoacetophenone (1.1 mmol, 1.1 equiv, 218.9 mg, 150.9 µL)
were added and stirred for 10 minutes at r.t, followed by the
addition of 3-bromopyridine (1.0 mmol, 1 equiv, 158.0 mg,
96.4 µL). The reaction vial was then secured with a Teflon seal
and a PEEK cap. The reaction mixture was subject to
microwave irradiation at 120 °C for 20 min. After cooling down
to room temperature, the reaction mixture was transferred to a
separatory funnel, followed by the addition of saturated NH4Cl
solution (2 mL). The mixture was extracted with ethyl acetate
three times (3 x 10 mL). The combined organic layer was dried
over anhydrous MgSO4. After rotatory evaporation to remove
the solvents, the product was purified using column
chromatography (0 – 100% ethyl acetate: hexanes). Yellow
1-(2,5-dimethylfuran-3-yl)-2-(pyridin-3-yl)ethanone (13b).
Synthesized from 3-acetyl-2,5-dimethylfuran (0.55 mmol, 1.1
equiv, 76.0 mg, 73.2 µL), and 3-iodopyridine (0.50 mmol, 1
equiv, 102.5 mg) according to the general procedure described
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above. brown oil. Yield, 127.6 mg, 59.3%. H NMR (CDCl3,
500 MHz, ppm): δ 8.50 (1H, d, J = 1.35 ), 8.47 (1H, s), 7.57
(1H, d, J = 7.75 Hz), 7.27 (1H, m), 6.25 (1H, s), 3.97 (2H, s),
2.53 (3H, s), 2.25 (3H, s). 13C{1H} NMR (CDCl3, 125 MHz,
ppm): δ 192.7, 158.3, 150.7, 150.4, 148.3, 137.3, 130.3, 123.5,
121.0, 105.6, 44.9, 14.4, 13.3. HRMS Calcd for C13H14NO2
[M+H] 216.1025. Found: 216.1021.
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solid. Yield, 146.3 mg, 53.0%. H NMR (CDCl3, 500 MHz,
ppm): δ 8.55 (1H, s), 8.00-7.95 (1H, m), 7.88 (2H, d, J = 8.2
Hz), 7.64 (2H, d, J = 8.2 Hz), 7.37 (1H, d, J = 8.2 Hz), 7.31 (1H,
dd, J = 7.3, 4.6 Hz), 4.30 (2H, s). 13C{1H} NMR (CDCl3, 125
MHz, ppm): δ 195.4, 150.2, 148.1, 137.8, 132.3, 132.2, 130.2,
130.1, 129.0, 123.8, 42.3. HRMS Calcd for C13H11NOBr
[M+H] 276.0024. Found: 276.0017.
1-(2,5-dimethylthiophen-3-yl)-2-(pyridin-3-yl)ethanone
(14b).14 Synthesized from 3-acetyl-2,5-dimethylthiophene
(0.55 mmol, 1.1 equiv, 84.8 mg, 78.1 µL), and 3-iodopyridine
(0.50 mmol, 1 equiv, 102.5 mg) according to the general
procedure described above. Brown oil. Yield, 182.0 mg, 78.7%.
1H NMR (CDCl3, 500 MHz, ppm): δ 8.50 (1H, d, J = 1.35), 8.50
(1H, d, J = 4.6), 8.47 (1H, s), 7.58 (1H, d, J = 7.75), 7.27-7.26
(1H, m), 4.09 (2H, s), 2.65 (3H, s), 2.41 (3H, s). 13C{1H} NMR
(CDCl3, 125 MHz, ppm): δ 192.3, 150.7, 149.1, 148.3, 137.3,
135.7, 134.7, 130.5, 125.8, 123.5, 45.3, 16.3, 15.1. HRMS
Calcd for C13H14NOS [M+H] 232.0796. Found: 232.0799.
3-methyl-1-(pyridin-3-yl)butan-2-one (9b). Synthesized from
3-methyl-2-butanone (0.55 mmol, 1.1 equiv, 47.4 mg, 58.8 µL),
and 3-iodopyridine (0.5 mmol, 1 equiv, 102.5 mg) according to
the general procedure described above. Yellow oil. Yield, 103.1
mg, 63.2%. 1H NMR (CDCl3, 500 MHz, ppm): δ 8.48 (1H, s),
8.40 (1H, s), 7.52 (1H, d, J = 7.8 Hz), 7.24-7.22 (1H, m), 3.74
(2H, s), 2.72 (1H, s), 0.12 (6H, d, J = 6.9 Hz). 13C{1H} NMR
(CDCl3, 125 MHz, ppm): 210.4, 150.5, 148.4, 137.2, 130.2,
123.5, 44.2, 40.8, 18.3. HRMS Calcd for C10H14NO [M+H]
164.1075. Found: 164.1082.
1-(pyridin-2-yl)-2-(pyridin-3-yl)ethanone (15b). Synthesized
from 2-acetylpyridine (0.55 mmol, 1.1 equiv, 66.7 mg, 61.1
µL), and 3-iodopyridine (0.50 mmol, 1 equiv, 102.5 mg)
according to the general procedure described above. Yellow oil.
Yield, 129.2 mg, 65.2%. 1H NMR (CDCl3, 500 MHz, ppm): δ
8.72 (1H, d, J = 3.6 Hz), 8.59 (1H, s), 8.50 (1H, d, J = 5.1 Hz),
8.05 (1H, d, J =7.8 Hz), 7.84 (1H, td, J = 7.8, 1.8 Hz), 7.71 (1H,
d, J = 7.8 Hz), 7.51 (1H, t, J = 5.1 Hz), 7.30-7.18 (2H, m), 4.51
(2H, s). 13C{1H} NMR (CDCl3, 125 MHz, ppm): δ 152.7,
150.4, 149.2, 147.5, 138.3, 137.2, 131.0, 127.7, 123.6, 122.5,
41.3. HRMS Calculated for C12H11N2O [M+H] 199.0871, found
199.0869.
4-methyl-1-(pyridin-3-yl)pentan-2-one (10b). Synthesized
from 4-methyl-2-pentadione (0.55 mmol, 1.1 equiv, 55.1 mg,
68.8 µL), and 3-iodopyridine (0.50 mmol, 1 equiv, 102.5 mg)
according to the general procedure described above. Yellow oil.
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Yield, 88.6 mg, 50.0%. H NMR (CDCl3, 500 MHz, ppm): δ
8.46 (1H, dd, J = 5.0, 1.4 Hz), 8.39 (1H, d, J = 1.8 Hz), 7.50
(1H, m), 7.21 (1H, m), 3.64 (2H, s), 2.33 (2H, d, J = 6.9 Hz),
2.11 (1H, m) 0.85(6H, d, J = 6.5 Hz). 13C{1H} NMR (CDCl3,
125 MHz, ppm): δ 206.8, 150.5, 148.4, 137.1, 129.9, 123.5,
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