The Journal of Organic Chemistry
Note
124.6 (d, JC−F = 20.5 Hz), 123.5; 19F NMR (CDCl3, 377 MHz) δ
−121.6; IR ν 3076, 1593, 1514, 1440, 1342, 1188, 1103 cm−1; MS m/z
(%) 218 (100) [M]+, 188 (38), 172 (35), 160 (19), 145 (20), 125
(17), 44 (15); HRMS (EI) m/z [M]+ calcd for C11H7FN2O2
218.0492; found 218.0486.
1575, 1507, 1436, 1283, 1240, 1185 cm−1; MS, m/z (%) 217 (67)
[M]+, 216 (28), 198 (77), 197 (100), 183 (25), 182 (24), 154 (23);
HRMS (EI) m/z [M]+ calcd for C13H12FNO 217.0903; found
217.0901.
3-Fluoro-2-(1-naphthalenyl)pyridine (3ap). Compound 3ap was
prepared following method A from potassium 3-fluoro-2-pyridinecar-
boxylate 1a (90.5 mg, 0.50 mmol) and 2-bromonaphthalene 2p (213
mg, 1.0 mmol). 3ap was isolated (SiO2, cyclohexane/ethyl acetate = 9/
1) as a colorless solid (82 mg, 74%): mp 93−94 °C; 1H NMR (CDCl3,
400 MHz) δ 8.59−8.68 (m, 1H), 7.89−8.03 (m, 2H), 7.76 (d, 1H, J =
8.0 Hz), 7.56−7.69 (m, 3H), 7.46−7.56 (m, 2H), 7.37−7.45 (m, 1H);
13C NMR (CDCl3, 101 MHz) δ 157.5 (d, JC−F = 257.9 Hz), 147.4 (d,
3-Fluoro-2-[3-(trifluoromethyl)phenyl]pyridine (3al) [CAS:
1261634-22-3]. Compound 3al was prepared following method A
from potassium 3-fluoro-2-pyridinecarboxylate 1a (90.5 mg, 0.50
mmol) and 1-bromo-3-(trifluoromethyl)benzene 2l (227 mg, 141 μL,
1.0 mmol). 3al was isolated (SiO2, cyclohexane/ethyl acetate = 9/1) as
1
a colorless oil (116 mg, 96%): H NMR (CDCl3, 400 MHz) δ 8.49−
8.61 (m, 1H), 8.30 (s, 1H), 8.19 (d, 1H, J = 7.8 Hz), 7.71 (d, 1H, J =
8.0 Hz), 7.62 (t, 1H, J = 7.8 Hz), 7.54 (ddd, J = 11.0, 8.3, 1.3 Hz),
J
C−F = 14.5 Hz), 145.4 (d, JC−F = 5.4 Hz), 133.7, 132.8 (d, JC−F = 3.6
7.29−7.39 (m, 1H); 13C NMR (CDCl3, 101 MHz): 157.6 (d, JC−F
=
Hz), 131.2, 129.5, 128.4, 127.9 (d, JC−F = 1.0 Hz), 126.5, 125.9, 125.2
261.6 Hz), 145.6 (d, JC−F = 5.4 Hz), 144.5 (d, JC−F = 10.9 Hz), 136.0
(d, JC−F = 5.5 Hz), 131.8−132.1 (m), 130.9 (q, JC−F = 31.8 Hz), 128.9,
125.7−125.9 (m), 125.5−125.7 (m), 124.4 (d, JC−F = 20.9 Hz), 124.2
(d, JC−F = 4.5 Hz), 123.9 (q, JC−F = 273.4 Hz); 19F NMR (CDCl3, 377
MHz) δ −62.6, −122.8; IR ν 3071, 1597, 1444, 1421, 1334, 1303,
1252, 1163, 1119, 1074 cm−1; MS, m/z (%) 241 (100) [M]+, 222
(d, JC−F = 1.8 Hz), 125.1, 123.9 (d, JC−F = 3.6 Hz), 123.6 (d, JC−F
=
20.0 Hz); 19F NMR (CDCl3, 377 MHz) δ −120.3; IR ν 3047, 3010,
1592, 1561, 1447, 1395, 1341, 1253, 1201 cm−1; MS, m/z (%) 223
+
(34) [M] , 222 (100), 221 (7), 111 (8), 50 (9); HRMS (EI) m/z
[M]+ calcd for C15H10FN 223.0797; found 223.0785.
3-Fluoro-2,2′-bipyridine (3aq) [CAS: 1863378-49-7]. Compound
3aq was prepared following method A from potassium 3-fluoro-2-
pyridinecarboxylate 1a (136 mg, 0.75 mmol) and 2-bromopyridine 2q
(80 mg, 48 μL, 0.5 mmol). 3aq was isolated (SiO2, cyclohexane/ethyl
acetate = 1/1) as a colorless oil (32 mg, 37%): 1H NMR (CDCl3, 200
MHz) δ 8.81 (d, 1H, J = 4.8 Hz), 8.59 (dt, 1H, Jd = 4.5 Hz, Jt = 1.5
Hz), 7.94−8.04 (m, 1H), 7.77−7.89 (m, 1H), 7.48−7.62 (m, 1H),
+
(20), 221 (19), 172 (25), 69 (16), 50 (12); HRMS (EI) m/z [M]
calcd for C12H7F4N 241.0515; found 241.0503.
3-Fluoro-2-(3-methoxyphenyl)pyridine (3am) [CAS: 1269225-56-
0]. Compound 3am was prepared following method A from 3-
fluoropyridinecarboxylate 1a (90.5 mg, 0.50 mmol) and 1-bromo-3-
methoxybenzene 2m (191 mg, 129 μL, 1.0 mmol). 3am was isolated
(SiO2, cyclohexane/ethyl acetate = 6/1) as an orange oil (99 mg,
97%). Compound 3am was prepared following method A from 3-
fluoropyridinecarboxylate 1a (90.5 mg, 0.50 mmol) and 1-chloro-3-
methoxybenzene 2m′ (145 mg, 125 μL, 1.0 mmol). 3am was isolated
(SiO2, cyclohexane/ethyl acetate = 6/1) as an orange oil (62 mg,
61%): 1H NMR (CDCl3, 400 MHz) δ 8.52−8.54 (m, 1H), 7.54−7.60
(m, 2H), 7.50 (ddd, 1H, J = 11.0, 8.3, 1.5 Hz), 7.41 (t, 1H, J = 7.9 Hz),
7.26−7.30 (m, 1H), 6.98−7.03 (m, 1H), 3.89 (s, 3H); 13C NMR
(CDCl3, 101 MHz) δ 159.7, 157.5 (d, JC−F = 260.4 Hz), 146.0 (d, JC−F
= 10.3 Hz), 145.3 (d, JC−F = 5.1 Hz), 136.6 (d, JC−F = 5.1 Hz), 129.4,
7.31−7.41 (m, 2H); 13C NMR (CDCl3, 101 MHz) δ 158.0 (d, JC−F
=
264.3 Hz), 153.5 (d, JC−F = 6.4 Hz), 149.6, 145.5 (d, JC−F = 5.5 Hz),
144.8 (d, JC−F = 9.1 Hz), 136.7, 124.9 (d, JC−F = 3.6 Hz), 124.7 (d,
JC−F = 20.9 Hz), 124.2 (d, JC−F = 5.4 Hz), 123.6; 19F NMR (CDCl3,
377 MHz) δ −122.5; IR ν 3059, 3011, 1585, 1454, 1422, 1256, 1196,
802 cm−1; MS, m/z (%) 174 (100) [M]+, 173 (33), 147 (20), 146
(20), 76 (15), 51 (26), 50 (25); HRMS (EI) m/z [M]+ calcd for
C10H7FN2 174.0593; found 174.0597.
3-(3-Fluoro-2-pyridinyl)quinoline (3ar). Compound 3ar was
prepared following method A from potassium 3-fluoro-2-pyridinecar-
boxylate 1a (90.5 mg, 0.50 mmol) and 3-bromoquinoline 2r (104 mg,
68 μL, 0.50 mmol). 3ar was isolated (SiO2, cyclohexane/ethyl acetate
= 4/1) as a colorless solid (70 mg, 62%): mp 138−139 °C; 1H NMR
(CDCl3, 200 MHz) δ 9.57 (s, 1H), 8.77−8.82 (m, 1H), 8.59−8.65 (m,
1H), 8.18 (d, 1H, J = 8.3 Hz), 7.95 (dd, 1H, J = 8.1, 1.5 Hz), 7.72−
7.84 (m, 1H), 7.52−7.66 (m, 2H), 7.31−7.43 (m, 1H); 13C NMR
(CDCl3, 50 MHz) δ 158.0 (d, JC−F = 261.3 Hz), 150.3 (d, JC−F = 6.6
Hz), 148.0, 145.8 (d, JC−F = 5.1 Hz), 143.6 (d, JC−F = 11.0 Hz), 136.0
(d, JC−F = 7.0 Hz), 130.2, 129.3, 128.6, 128.2 (d, JC−F = 5.9 Hz), 127.5,
126.9, 124.3 (d, JC−F = 16.8 Hz), 124.1 (d, JC−F = 4.0 Hz); 19F NMR
(CDCl3, 377 MHz) δ −122.3; IR ν 3061, 3038, 1595, 1410, 1344,
1113 cm−1; MS, m/z (%) 224 (100) [M]+, 223 (45), 205 (10), 122
(10), 76 (10), 50 (14); HRMS (EI) m/z [M]+ calcd for C14H9FN2
224.0750; found 224.0739.
124.1 (d, JC−F = 21.3 Hz), 123.5 (d, JC−F = 3.7 Hz), 121.3 (d, JC−F
=
7.3 Hz), 115.4, 113.8 (d, JC−F = 5.1 Hz), 55.3; 19F NMR (CDCl3, 377
MHz) δ −122.4; IR ν 3068, 2935, 2836, 1585, 1463, 1439, 1417, 1288,
1253, 1229 cm−1; MS, m/z (%) 203 (97) [M]+, 202 (100), 174 (39),
173 (27), 172 (46), 159 (14); HRMS (EI) m/z [M]+ calcd for
C12H10FNO 203.0746; found 203.0744.
2-[3-(tert-Butyl)phenyl]-3-fluoropyridine (3an). Compound 3an
was prepared following method A from 3-fluoro-2-pyridinecarboxylate
1a (90.5 mg, 0.50 mmol) and 1-bromo-3-(1,1-dimethylethyl)benzene
2n (213 mg, 170 μL, 1.0 mmol). 3an was isolated (SiO2, cyclohexane/
1
ethyl acetate = 9/1) as a colorless liquid (61 mg, 53%): H NMR
(CDCl3, 400 MHz) δ 8.54 (dt, 1H, Jd = 4.5 Hz, Jt = 1.5 Hz), 8.00 (d,
1H, J = 1.5 Hz), 7.76 (dq, 1H, Jd = 7.5 Hz, Jq = 1.6 Hz), 7.40−7.53 (m,
3H), 7.23−7.30 (m, 1H), 1.40 (s, 9H); 13C NMR (CDCl3, 101 MHz)
δ 157.5 (d, JC−F = 262.5 Hz), 151.3, 146.8 (d, JC−F = 10.9 Hz), 145.1
(d, JC−F = 5.4 Hz), 134.7 (d, JC−F = 4.5 Hz), 128.1, 126.4, 126.0 (d,
JC−F = 5.4 Hz), 125.8 (d, JC−F = 4.5 Hz), 124.1 (d, JC−F = 20.9 Hz),
123.3 (d, JC−F = 3.6 Hz), 34.8, 31.3; 19F NMR (CDCl3, 377 MHz) δ
−122.9; IR ν 3064, 2963, 2868, 1596, 1438, 1409, 1364, 1249 cm−1;
MS, m/z (%) 229 (28) [M]+, 215 (15), 214 (100), 199 (11), 185
(10), 43 (15); HRMS (EI) m/z [M]+ calcd for C15H16FN 229.1267;
found 229.1285.
3-Fluoro-2-(3-thienyl)pyridine (3as). Compound 3as was prepared
following method A from potassium 3-fluoro-2-pyridinecarboxylate 1a
(90.5 mg, 0.50 mmol) and 3-bromothiophene 2s (168 mg, 97 μL, 1.0
mmol). 3as was isolated (SiO2, cyclohexane/ethyl acetate = 9/1) as a
1
colorless oil (50 mg, 56%): H NMR (CDCl3, 200 MHz) δ 8.46 (dt,
1H, Jd = 4.5 Hz, Jt = 1.6 Hz), 8.04−8.12 (m, 1H), 7.86 (dt, 1H, Jd = 5.1
Hz, Jt = 1.3 Hz), 7.36−7.53 (m, 2H), 7.14−7.25 (m, 1H); 13C NMR
(CDCl3, 50 MHz) δ 156.8 (d, JC−F = 260.5 Hz), 145.1 (d, JC−F = 4.8
Hz), 142.1 (d, JC−F = 11.0 Hz), 136.9 (d, JC−F = 6.2 Hz), 127.6 (d, JC−F
= 4.8 Hz), 126.2 (d, JC−F = 11.0 Hz), 125.3 (d, JC−F = 1.5 Hz), 123.7
(d, JC−F = 20.5 Hz), 122.7 (d, JC−F = 4.0 Hz); 19F NMR (CDCl3, 377
MHz) δ −121.4; IR ν 3113, 3065, 3021, 1597, 1454, 1440, 1206, 1099
cm−1; MS, m/z (%) 179 (100) [M]+, 178 (26), 160 (37), 135 (10),
107 (10), 45 (11); HRMS (EI) m/z [M]+ calcd for C9H6FNS
179.0205; found 179.0208.
3-Fluoro-2-(5-methoxy-2-methylphenyl)pyridine (3ao). Com-
pound 3ao was prepared following method A from potassium 3-
fluoro-2-pyridinecarboxylate 1a (90.5 mg, 0.50 mmol) and 1-bromo-4-
methoxy-2-methylbenzene 2o (207 mg, 228 μL, 1.0 mmol). 3ao was
isolated (SiO2, cyclohexane/ethyl acetate = 9/1) as a yellow oil (98
mg, 90%): 1H NMR (CDCl3, 400 MHz) δ 8.41−8.47 (m, 1H), 7.36−
7.45 (m, 1H), 7.19−7.29 (m, 2H), 6.74−6.81 (m, 2H), 3.78 (s, 3H),
2.20 (s, 3H); 13C NMR (CDCl3, 101 MHz) δ 159.9, 157.0 (d, JC−F
=
3-Fluoro-2-(2-thienyl)pyridine (3at). Compound 3at was prepared
following method A from potassium 3-fluoropyridinecrboxylate 1a
(90.5 mg, 0.50 mmol) and 2-bromothiophene 2t (166 mg, 99 μL, 1.0
mmol). 3at was isolated (SiO2, cyclohexane/ethyl acetate = 9/1) as a
256.1 Hz), 148.1 (d, JC−F = 14.5 Hz), 145.1 (d, JC−F = 5.4 Hz), 138.3,
131.1 (d, JC−F = 1.8 Hz), 127.6 (d, JC−F = 3.6 Hz), 123.3 (d, JC−F = 2.7
Hz), 123.2 (d, JC−F = 14.5 Hz), 115.7, 111.2, 55.2, 19.9; 19F NMR
(CDCl3, 377 MHz) δ −121.2; IR ν 3061, 3002, 2930, 2835, 1608,
1
colorless solid (56 mg, 63%): mp 43−44 °C; H NMR (CDCl3, 200
F
J. Org. Chem. XXXX, XXX, XXX−XXX