1354
Y. Hajbi et al.
PAPER
6-Phenyl-2-(trityloxymethyl)-2,3-dihydrofuro[2,3-b]pyridine
(16)
Purification by column chromatography (silica gel, PE–EtOAc,
6:4).
tion was quenched with H2O (40 mL) and the mixture was extracted
with EtOAc (3 × 60 mL). The organic layer was dried (MgSO4),
evaporated, and purified by column chromatography (silica gel,
PE–EtOAc, 4:6); this afforded 19.
Yield: 83%; yellow oil.
Yield: 81%; yellow solid; mp 74–76 °C.
IR (NaCl): 3018, 1606, 1437, 1337, 1214, 1015, 984, 764, 680 cm–1.
IR (KBr): 3019, 1571, 1414, 1382, 1215, 998, 748, 668 cm–1.
1H NMR (250 MHz, CDCl3): d = 8.03–7.97 (m, 2 H), 7.38–7.20
(m, 20 H), 5.03–4.93 (ddd, J = 4.7, 5.9, 9.7 Hz, 1 H), 3.43 (dd,
J = 4.4, 10.0 Hz, 1 H), 3.33 (dd, J = 5.0, 10.0 Hz, 1 H), 3.26 (dd,
J = 9.4, 16.3 Hz, 1 H), 3.05 (dd, J = 5.9, 16.3 Hz, 1 H).
1H NMR (250 MHz, CDCl3): d = 9.44 (s, 1 H), 8.16–8.20 (m, 2 H),
7.56–7.59 (m, 3 H), 4.87 (dd, J = 3.5, 12.3 Hz, 1 H), 4.51 (dd,
J = 6.0, 12.3 Hz, 1 H), 3.49–3.53 (m, 1 H), 2.90 (t, J = 4.6 Hz, 1 H),
2.83 (dd, J = 2.6, 4.6 Hz, 1 H).
13C NMR (62.9 MHz, CDCl3): d = 168.5 (C), 155.2 (C), 143.8
(CAr), 139.1 (CAr), 133.9 (CH), 129.6 (CHAr), 128.8 (CHAr), 128.6
(CHAr), 127.9 (CHAr), 127.1 (CHAr), 126.9 (CHAr), 118.4 (C), 113.3
(CH), 86.7 (CHO), 79.9 (CO), 65.9 (CH2O), 30.8 (CH2).
13C NMR (62.9 MHz, CDCl3): d = 165.4 (C), 158.4 (C), 142.2
(CAr), 133.2 (CHAr), 129.7 (CHAr), 128.2 (CHAr), 126.2 (CH), 69.5
(CH2), 49.7 (CHO), 45.2 (CH2).
MS (ES): m/z = 230 [M + H].
MS (ES): m/z = 470 [M + H].
ESI-HRMS: m/z [M + H] calcd for C12H12N3O2: 230.0930; found:
ESI-HRMS: m/z [M + H] calcd for C33H28NO2: 470.2120; found:
230.0916.
470.2124.
1-(5-Phenyl-1,2,4-triazin-3-yloxy)dec-4-yn-2-ol (20)
2-(Trityloxymethyl)-2,3-dihydrofuro[2,3-b]pyridine (17)
Purification by column chromatography (silica gel, PE–EtOAc,
9:1).
A dry and argon-flushed flask equipped with a magnetic stirrer and
a septum was charged with 2 M Me3Al in toluene (873 mL, 1.7
mmol). Et3N (24 mL, 0.2 mmol) was added at r.t. After 5 min, the
alkyne (1.9 mmol) was then added dropwise, and the resulting mix-
ture was heated to 60 °C for 4 h. The soln was then added by syringe
to a soln of oxirane 19 (200 mg, 0.9 mmol) in anhyd toluene (10
mL) at 0 °C; the reaction mixture was stirred for 1 h at the same
temperature, then allowed to slowly reach r.t., and stirred for 1 h be-
fore being poured into a cooled 2 M aq soln of Rochelle’s salts (15
mL) (CAUTION: gas evolution). After 30 min of vigorous stirring,
the organic phase was separated and the aqueous phase was extract-
ed with Et2O (3 × 15 mL). The organic layer was dried (MgSO4),
the solvent was evaporated, and the crude residue was purified by
column chromatography (silica gel, PE–EtOAc, 8:2); this afforded
compound 20.
Yield: 90%; orange oil.
IR (KBr): 2927, 1435, 1248, 1202, 1054, 917, 842, 768, 672 cm–1.
1H NMR (250 MHz, CDCl3): d = 7.90–7.82 (m, 2 H), 7.28 (dd,
J = 1.4, 7.9 Hz, 6 H), 7.21–7.09 (m, 9 H), 6.37–6.29 (m, 1 H), 4.90–
4.81 (m, 1 H), 3.28 (d, J = 4.5 Hz, 2 H), 3.11 (dd, J = 10.0, 16.1 Hz,
1 H), 2.95 (dd, J = 9.8, 16.0 Hz, 1 H).
13C NMR (62.9 MHz, CDCl3): d = 165.4 (C), 144.1 (CH), 143.2
(CAr), 136.5 (CH), 130.9 (C), 129.1 (CHAr), 128.7 (CHAr), 126.7
(CHAr), 112.4 (CH), 106.4 (CHO), 68.5 (CH2O), 48.9 (CO), 32.0
(CH2).
MS (ES): m/z = 394 [M + H].
Yield: 36%; yellow oil.
IR (NaCl): 3422, 2954, 2187, 1666, 1542, 1425, 1256, 1014, 796,
668 cm–1.
[6-Phenyl-4-(trimethylsilyl)-2,3-dihydrofuro[2,3-b]pyridin-2-
yl]methanol (18)
1H NMR (250 MHz, CDCl3): d = 9.43 (s, 1 H), 8.18–8.15 (m, 2 H),
7.64–7.51 (m, 3 H), 4.79–4.63 (ddd, J = 3.9, 6.4, 11.2 Hz, 2 H,),
4.27 (s, 1 H), 3.07 (s, 1 H, OH), 2.62 (dd, J = 2.2, 8.6 Hz, 2 H), 2.13
(t, J = 2.2 Hz, 2 H), 1.52–1.46 (m, 2 H), 1.39–1.25 (m, 4 H), 0.87 (t,
J = 7.0 Hz, 3 H).
13C NMR (62.9 MHz, CDCl3): d = 165.5 (C), 158.2 (C), 141.8
(CH), 133.0 (CAr), 133.0 (CHAr), 129.5 (CHAr), 128.0 (CHAr), 83.8
(C), 74.8 (C), 71.4 (CH2O), 68.7 (CHOH), 31.2 (CH2), 28.7 (CH2),
24.1 (CH2), 22.3 (CH2), 18.8 (CH2), 14.0 (C H3).
TFA (110 mL, 1.4 mmol) was added to a stirred soln of 12 (155 mg,
0.3 mmol) in anhyd CH2Cl2 under a a N2 atmosphere. The mixture
was stirred at r.t. for 48 h. Then the reaction was quenched with H2O
(10 mL) and the mixture was extracted with CH2Cl2 (3 × 10 mL).
The combined organic extracts were dried (MgSO4), evaporated,
and purified by column chromatography (silica gel, PE–EtOAc,
9:1); this afforded the desired product 18.
Yield: 63%; yellow oil.
IR (NaCl): 3440, 3360, 3254, 3010, 1466, 1438, 1315, 1208, 1025,
981, 763, 682 cm–1.
MS (ES): m/z = 326 [M + H].
1H NMR (250 MHz, CDCl3): d = 7.92 (dd, J = 1.8, 8.3 Hz, 2 H),
7.46–7.34 (m, 3 H), 7.32 (s, 1 H), 5.02–4.91 (m, 1 H), 3.92 (dd,
J = 3.2, 5.7 Hz, 1 H), 3.73 (dd, J = 5.7, 12.3 Hz, 1 H), 3.26 (dd,
J = 9.5, 16.3 Hz, 1 H), 3.07 (dd, J = 7.4, 16.3 Hz, 1 H), 0.34 (s, 9 H).
13C NMR (62.9 MHz, CDCl3): d = 166.8 (C), 154.2 (C-Si), 148.3
(C), 139.2 (CAr), 128.7 (CHAr), 128.6 (CHAr), 126.9 (CHAr), 123.1
(C), 118.1 (CH), 80.9 (CHO), 64.9 (CH2OH), 30.7 (CH2), –1.31
(CH3Si).
ESI-HRMS: m/z [M + Na] calcd for C19H23N3O2Na: 348.1688;
found: 348.1673.
5-Pentyl-7-phenyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-3-ol
(21)
Triazine 20 (0.98 g, 0.3 mmol) was dissolved in chlorobenzene (2
mL) and heated at 180 °C under microwave irradiation (pressure of
up to 3–6 bar possible). The reaction was monitored by TLC. After
complete conversion of the starting material, the product was puri-
fied by column chromatography (silica gel, PE–EtOAc, 5:5).
MS (ES): m/z = 300 [M + H].
Yield 96%; yellow-orange oil.
3-(Oxiranylmethoxy)-5-phenyl-1,2,4-triazine (19)
Glycidol (367 mL, 5.5 mmol) was added to a stirred suspension of
NaH (60% oil dispersion; 0.22 g, 5.5 mmol) under a N2 atmosphere
at 0 °C. After 10 min, the 5-phenyl-1,2,4-triazine 1 (1 g, 4.2 mmol)
was added. The mixture was then warmed to r.t. and monitored by
TLC. After complete conversion of the starting material, the reac-
IR (NaCl): 3400, 3260, 2960, 1730, 1680, 1458, 1284, 1215, 1098,
1022, 964, 784 cm–1.
1H NMR (250 MHz, CDCl3): d = 7.93–7.90 (m, 2 H), 7.43–7.33 (m,
3 H), 7.07 (s, 1 H), 5.01–4.91 (m, 1 H), 3.92 (dd, J = 7.3, 11.9 Hz,
1 H), 3.75 (dd, J = 5.0, 11.9 Hz, 1 H), 3.20 (dd, J = 9.4, 16.3 Hz, 1
Synthesis 2010, No. 8, 1349–1355 © Thieme Stuttgart · New York