7
56
P. Gros, Y. Fort
SHORT PAPER
1
3
C NMR: d = 9.6, 13.4, 27, 28.7, 52.8, 108.6, 125.6, 135.5, 162.8,
3-(6-Methoxy-2-pyridyl)quinoline (4e)
Mp 87 °C.
1
70.3.
1
H NMR: d = 4.07 (s, 3H), 6.75 (d, J = 8 Hz, 1H), 7.45 (d, J = 7.5
Hz, 1H), 7.53 (dt, J = 7, 1 Hz, 1H), 7.65 (dt, J = 7.5, 0.5 Hz, 1H),
Coupling with 2-Methoxy-6-(tributylstannyl)pyridine (2)
Method A
7
.70 (dt, J = 7.5, 0.5 Hz, 1H), 7.89 (d, J = 8 Hz, 1H), 8.14 (d, J = 8.5
To
a solution of isolated 2-methoxy-6-tributyltinpyridine 2
Hz, 1H), 8.70 (d, J = 1.8 Hz, 1H), 9.60 (d, J = 2.2 Hz, 1H).
13
(
(
796 mg, 2 mmoles) in toluene (20 mL) were added Pd(PPh3)4
115 mg, 0.1 mmol, 5mol%) and the appropriate triflate or halide (2
C NMR: d = 53.8, 110.6, 113.5, 127.3, 128.2, 128.8, 129.6,
30.15, 131.9, 133.7, 139.7, 148.5, 149.8, 152.4, 164.4.
1
mmoles). The mixture was refluxed for 12 h. After cooling at r.t. the
mixture was poured into a sat. KF (25 mL). The organic layer was
then separated, washed with H O (25 mL) and dried (MgSO ). After
evaporation of the solvent, the crude product was purified on a chro-
matotron using hexane/EtOAc mixtures as eluents.
+
+
+–
MS (EI) m/z = 237 (15, M +1), 236 (100, M ), 235 (91, M 1), 207
(22), 192 (5), 177 (3), 151 (4), 140 (3), 118 (8), 103 (7), 89 (6), 76
(10), 63 (4), 51 (3).
2
4
4
-(6-Methoxy-2-pyridyl)isoquinoline (4f)
Mp 95 °C.
Coupling with 2-Methoxy-6-(tributylstannyl)pyridine (2)
Method B
The solution of 2 in hexane/THF was heated to 25 °C and Pd(PPh3)4
1
H NMR: d = 3.99 (s, 3H), 6.84 (d, J = 8.5 Hz, 1H), 7.22 (d, J = 7
Hz, 1H), 7.62 (dt, J = 7, 0.8 Hz, 1H), 7.71 (dt, J = 7, 1.5 Hz, 1H),
7
8
.73 (t, J = 7.5 Hz, 1H), 8.04 (d, J = 8 Hz, 1H), 8.37 (d, 8.5 Hz, 1H),
.70 (s, 1H), 9.30 (s, 1H).
(
(
230 mg, 0.2 mmol, 5mol%) and the appropriate triflate or halide
10 mmoles) were added. The mixture was refluxed for 18 h. After
1
3
cooling at r.t. the mixture was poured into a sat. KF (25 mL). The
C NMR: d = 53.9, 110.3, 118.1, 125.4, 127.6, 128.3, 129.0, 131.0,
organic layer was then separated, washed with H O (25 mL) and
131.8, 134.2, 139.6, 143.9, 153.4, 154.2, 164.2.
2
dried (MgSO ). After evaporation of the solvent, the crude product
was purified on a chromatotron using hexane/EtOAc mixtures as
eluents.
+
+
+
4
MS (EI) m/z 237 (14, M +1), 236 (94, M ), 235 (100, M –1), 221
26), 205 (23), 192 (17), 151 (6), 76 (10), 63 (4), 51 (2).
(
Coupling with 6-Bromozinc-2-methoxypyridine (3)
A solution of 2-(dimethylamino)ethanol (720 mg, 8 mmoles) in
hexane (5mL) was cooled at ca –5 °C and BuLi was (10 mL, 16
References
(1) Fort, Y.; Becker, S.; Caubère, P. Tetrahedron 1994, 41,
11893.
mmols) was added dropwise under N . After 30 min at 0 °C, a solu-
2
Fort, Y. Tetrahedron Lett. 1995, 36, 6051.
2) Brenner, E.; Fort, Y. Tetrahedron Lett. 1998, 39, 5359.
3) (a) Gros, Ph.; Fort, Y.; Caubère P. J. Chem. Soc. Perkin Trans.
I 1997, 20, 3071.
tion of 2-methoxypyridine (430 mg, 4 mmols) in hexane (5 mL) was
added dropwise. After 1 h a deep green color was observed. The so-
lution was cooled at –78 °C and a solution of anhyd ZnBr (2.24 g,
(
(
2
1
–
0 mmols) in THF (20mL) was added dropwise. After 30 min at
78 °C and 30 min at r.t., Pd(PPh ) (140 mg, 0.12 mmol, 3mol%)
(
b) Gros, Ph.; Fort, Y.; Caubère P. J. Chem. Soc. Perkin Trans.
I 1997, 24, 3597.
c) Gros, Ph.; Fort, Y; J. Chem. Soc. Perkin Trans. I 1998, 21,
515.
4) (a) Yamamoto, Y.; Azuma, Y.; Mitoh, H. Synthesis 1986, 564
b) Bell, A.; Roberts, D.; Ruddock, K. Tetrahedron Lett. 1988,
9, 5013.
c) Trecourt, F.; Gervais, B.; Mallet, M.; Queguiner, G. J. Org.
3
4
and the appropriate triflate or halide (10 mmols) were added. The
mixture was refluxed for 12 h. After cooling at r.t. the mixture was
(
3
quenched with a sat. NH Cl (25 mL). The organic layer was then
4
(
separated, washed with H O (25 mL) and dried (MgSO ). After
2
4
(
3
(
evaporation of the solvent, the crude product was purified on a chro-
matotron using hexane/EtOAc mixtures as eluents.
Chem. 1996, 61, 1673.
8
6
(
ples.
-methoxy-2,2'-bipyridine (4a) and 6-methoxy-2,3'-bipyridine
(d) Jetter, M.; Reitz, A. Synthesis 1998, 829.
(e) Miller, J.; Farrell, R. Tetrahedron Lett. 1998, 39, 6441.
(f) Schmidt, B.; Neitemeier, V. Synthesis 1998, 42.
5) Knochel, P.; Singer, R. Chem.Rev. 1993, 93, 2117 and refe-
rences cited therein.
6) Stille, J. K. Pure Appl. Chem. 1985, 57, 1771 and references
cited therein.
7) Keumi, T.; Yoshimura, K.; Shimada, M.; Kitajima, H. Bull.
Chem. Soc. Jpn. 1988, 61, 455.
9
4b) were found identical (spectroscopic data) to authentic sam-
(
(
(
(
(
2
-(6-Methoxy-2-pyridyl)pyrimidine (4c)
Oil, H NMR: d = 4.09 (s, 3H), 6.87 (dd, 8.75, J = 0.75 Hz, 1H), 7.25
t, J = 4.8 Hz, 1H), 7.70 (dt, 7.5, J = 0.75 Hz, 1H), 8.06 (dd, J = 7,
1
(
0
.75 Hz, 1H), 8.87 (d, J = 4.5 Hz, 2H).
1
3
C NMR: d = 53.9, 113.2, 117.5, 120.4, 139.6, 152.8, 157.9, 164.2,
1
64.7.
8) Pojer, P. M.; Summers, L. A. J. Heterocycl. Chem. 1974, 11,
303.
9) Dehmlow, E.; Sleeger, A. Liebigs Ann.Chem. 1992, 9, 953.
+
+
+
MS (EI) m/z 188 (6, M +1), 187 (58, M ), 186 (100, M -1), 156
32), 130 (11), 104 (11), 93 (7), 78 (8), 53 (6).
(
5
-(6-Methoxy-2-pyridyl)pyrimidine (4d)
Mp 120 °C.
Article Identifier:
1437-210X,E;1999,0,05,0754,0756,ftx,en;Z08698SS.pdf
1
H NMR: d = 4.03 (s, 3H), 6.80 (d, J = 8 Hz, 1H), 7.37 (d, J = 7.5
Hz, 1H), 7.70 (dt, J = 7, 0.8 Hz, 1H), 9.23 (s, 1H), 9.35 (s, 2H).
1
3
C NMR: d = 53.9, 111.8, 113.4, 132.4, 139.9, 149.5, 155.3, 158.8,
+
+
1
64.6, MS (EI) m/z 188 (10, M +1), 187 (100, M ), 186 (70,
+
M –1), 159 (33), 143 (14), 132 (12), 130 (17), 103 (12), 76 (15), 63
8), 51 (8).
(
Synthesis 1999, No. 5, 754 –756 ISSN 0039-7881 © Thieme Stuttgart · New York