The Journal of Organic Chemistry
Article
13C{1H} NMR (100 MHz, CDCl3) δ 198.0, 175.8, 136.5, 136.0, 133.2,
128.6, 128.5, 128.1, 128.0, 127.9, 66.4, 41.8, 34.9, 17.3; HRMS (ESI)
m/z [M + H]+ calcd for C18H19O3+ 283.1329, found 283.1327; HRMS
7.21 (m, 2H), 2.78 (s, 2H), 2.39 (s, 3H), 1.24 (s, 6H); 13C{1H} NMR
(100 MHz, CDCl3) δ 173.4, 150.9, 140.0, 133.2, 129.3, 125.7, 37.1,
34.0, 23.9, 21.3; HRMS (ESI) m/z [M + H]+ calcd for C13H17N2O+
217.1335, found 217.1332.
+
(ESI) m/z [M + Na]+ calcd for C18H18NaO3 305.1148, found
6-(4-Fluorophenyl)-4,4-dimethyl-4,5-dihydropyridazin-3(2H)-
one (5c): white solid; Rf = 0.30 (ethyl acetate/petroleum ether = 1:5)
(1.0 mmol scale, 128.0 mg, 58% yield); mp 145−147 °C; ATR-FTIR
(cm−1) 3223, 3096, 2968, 2920, 1655, 1611, 1507, 1336, 840, 776, 564;
1H NMR (400 MHz, CDCl3) δ 8.66 (br, s, 1H), 7.73−7.68 (m, 2H),
305.1142.
Ethyl 2-Methyl-4-oxo-4-phenylbutanoate (4d):.5a,11e yellow oil; Rf
= 0.30 (ethyl acetate/petroleum ether = 1:15) (0.6 mmol scale, 91.2
mg, 69% yield) ATR-FTIR (cm−1) 2978, 1728, 1684, 1449, 1212, 1172,
754, 690; 1H NMR (400 MHz, CDCl3) δ 7.98−7.95 (m, 2H), 7.58−
7.54 (m, 1H), 7.48−7.44 (m, 2H), 4.14 (q, J = 7.2 Hz, 2H), 3.48 (dd, J =
7.8 Hz, 17.5 Hz, 1H), 3.15−3.06 (m, 1H), 3.01 (dd, J = 5.4 Hz, 17.5 Hz,
1H), 1.26 (t, J = 7.2 Hz, 3H), 1.24 (t, J = 7.2 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 198.1, 176.0, 136.6, 133.1, 128.5, 128.0, 60.6,
41.9, 35.0, 17.3, 14.1.
7.13−7.07 (m, 2H), 2.77 (s, 2H), 1.24 (s, 6H); 13C{1H} NMR (100
1
MHz, CDCl3) δ 173.2, 163.6 (d, JC−F = 248.7 Hz), 149.7, 132.2 (d,
4JC−F = 3.4 Hz), 127.7 (d, 3JC−F = 8.6 Hz), 115.7 (d, 2JC−F = 21.8 Hz),
37.1, 34.0, 23.9; 19F NMR (376 MHz, CDCl3) δ −110.87 to −110.94
(m, 1F); HRMS (ESI) m/z [M + H]+ calcd for C12H14FN2O+
221.1085, found 221.1083.
Ethyl 2-Ethyl-4-oxo-4-phenylbutanoate (4e): yellow oil; Rf = 0.30
(ethyl acetate/petroleum ether = 1:15) (0.6 mmol scale, 104.0 mg, 74%
yield) ATR-FTIR (cm−1) 2967, 1726, 1684, 1448, 1210, 1163, 1028,
755, 689; 1H NMR (400 MHz, CDCl3) δ 7.98−7.95 (m, 2H), 7.58−
7.54 (m, 1H), 7.47−7.43 (m, 2H), 4.21−4.09 (m, 2H), 3.49−3.42 (m,
1H), 3.06−2.94 (m, 2H), 1.76−1.62 (m, 2H), 1.25 (t, J = 7.2 Hz, 3H),
0.97 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 198.3,
175.3, 136.6, 133.1, 128.5, 128.0, 60.4, 41.7, 39.9, 25.2, 14.2, 11.5;
6-(4-Chlorophenyl)-4,4-dimethyl-4,5-dihydropyridazin-3(2H)-
one (5d): white solid; Rf = 0.35 (ethyl acetate/petroleum ether = 1:5)
(1.0 mmol scale, 157.0 mg, 66% yield); mp 146−148 °C; ATR-FTIR
(cm−1) 3205, 3087, 2966, 2928, 1667, 1610, 1330, 1237, 1092, 828,
1
805, 753, 623, 584, 552; H NMR (400 MHz, CDCl3) δ 8.66 (br, s,
1H), 7.67−7.64 (m, 2H), 7.40−7.37 (m, 2H), 2.77 (s, 2H), 1.24 (s,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 173.2, 149.6, 135.8, 134.4,
128.8, 127.0, 36.9, 34.0, 23.9; HRMS (ESI) m/z [M + H]+ calcd for
C12H14ClN2O+ 237.0789, found 237.0786.
6-(4-Methoxyphenyl)-4,4-dimethyl-4,5-dihydropyridazin-3(2H)-
one (5e): white solid; Rf = 0.20 (ethyl acetate/petroleum ether = 1:5)
(1.0 mmol scale, 130.0 mg, 56% yield); mp 161−164 °C; ATR-FTIR
(cm−1) 3203, 3092, 2930, 1672, 1614, 1600, 1510, 1460, 1333, 1251,
1170, 819, 797, 559, 543; 1H NMR (400 MHz, CDCl3) δ 8.65 (br, s,
1H), 7.69−7.65 (m, 2H), 6.95−6.91 (m, 2H), 3.84 (s, 3H), 2.76 (s,
2H), 1.23 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 173.4, 160.9,
150.6, 128.6, 127.3, 113.9, 55.4, 37.0, 34.0, 23.9; HRMS (ESI) m/z [M
+ H]+ calcd for C13H17N2O2+ 233.1285, found 233.1278.
+
HRMS (ESI) m/z [M + H]+ calcd for C14H19O3 235.1329, found
235.1330; HRMS (ESI) m/z [M + Na]+ calcd for C14H18NaO3
+
257.1148, found 257.1143.
Ethyl 2-(2-Oxo-2-phenylethyl)pentanoate (4f): yellow oil; Rf = 0.30
(ethyl acetate/petroleum ether = 1:15) (0.6 mmol scale, 106.5 mg, 72%
yield) ATR-FTIR (cm−1) 2959, 2933, 1728, 1686, 1448, 1213, 1170,
754, 690; 1H NMR (400 MHz, CDCl3) δ 7.98−7.95 (m, 2H), 7.57−
7.53 (m, 1H), 7.47−7.43 (m, 2H), 4.20−4.09 (m, 2H), 3.49−3.42 (m,
1H), 3.07−3.00 (m, 2H), 1.73−1.64 (m, 1H), 1.60−1.51 (m, 1H),
1.43−1.33 (m, 2H), 1.25 (t, J = 7.2 Hz, 3H), 0.93 (t, J = 7.2 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 198.3, 175.7, 136.6, 133.1, 128.5,
8-Phenyl-6,7-diazaspiro[3.5]non-7-en-5-one (5f): white solid; Rf =
0.35 (ethyl acetate/petroleum ether = 1:5) (1.0 mmol scale, 118.2 mg,
55% yield); mp 155−157 °C; ATR-FTIR (cm−1) 3222, 3094, 2950,
2923, 1660, 1336, 1241, 753, 682; 1H NMR (400 MHz, CDCl3) δ 8.62
(br, s, 1H), 7.75−7.71 (m, 2H), 7.46−7.40 (m, 3H), 3.09 (s, 2H),
2.62−2.55 (m, 2H), 2.10−2.00 (m, 2H), 1.91−1.84 (m, 2H); 13C{1H}
NMR (100 MHz, CDCl3) δ 172.1, 150.7, 136.1, 129.8, 128.6, 125.7,
38.8, 34.4, 28.7, 15.2; HRMS (ESI) m/z [M + H]+ calcd for
C13H15N2O+ 215.1179, found 215.1173.
tert-Butyl((1-(4-((tert-butyldimethylsilyl)oxy)phenyl)vinyl)oxy)-
dimethylsilane (6a): pale yellow oil; Rf = 0.50 (NEt3/petroleum ether
= 1:50) (10 mmol scale, 3.06 g, 84% yield) ATR-FTIR (cm−1) 2955,
2930, 2857, 1604, 1506, 1253, 1004, 912, 830, 777, 682; 1H NMR (400
MHz, CDCl3) δ 7.50−7.46 (m, 2H), 6.80−6.77 (m, 2H), 4.77 (d, J =
1.6 Hz, 1H), 4.31 (d, J = 1.6 Hz, 1H), 1.00 (s, 9H), 0.98 (s, 9H), 0.20 (s,
6H), 0.19 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 155.8, 155.7,
130.9, 126.5, 119.5, 89.2, 25.8, 25.6, 18.3, 18.2, −4.4, −4.7; HRMS
(ESI) m/z [M + H]+ calcd for C20H37O2Si2+ 365.2327, found 365.2316.
Ethyl (R)-2,2-Dimethyl-4-(4-(3-(2-methylpyrrolidin-1-yl)propoxy)-
phenyl)-4-oxobutanoate (6d):3a pale yellow oil; Rf = 0.45 (MeOH/
DCM = 1:10) (2.0 mmol scale, 287.0 mg, 38% yield) ATR-FTIR
(cm−1) 2963, 1723, 1675, 1598, 1234, 1170, 1125, 827, 732; 1H NMR
(400 MHz, CDCl3) δ 7.90−7.86 (m, 2H), 6.91−6.87 (m, 2H), 4.10 (q,
J = 7.2 Hz, 2H), 4.09−4.05 (m, 2H), 3.30−3.24 (m, 1H), 3.22 (s, 2H),
3.08−3.01 (m, 1H), 2.53−2.44 (m, 1H), 2.36−2.30 (m, 1H), 2.28−
2.21 (m, 1H), 2.13−2.02 (m, 2H), 2.01−1.92 (m, 1H), 1.90−1.69 (m,
2H), 1.55−1.45 (m, 1H), 1.28 (s, 6H), 1.18 (t, J = 7.2 Hz, 3H), 1.15 (d,
J = 6.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.1, 177.4,
162.7, 130.1, 130.0, 114.0, 66.3, 60.9, 60.4, 53.8, 50.6, 48.0, 39.9, 32.4,
27.8, 25.7, 21.4, 18.3, 14.0.
128.0, 60.4, 40.4, 40.1, 34.3, 20.3, 14.2, 13.9; HRMS (ESI) m/z [M +
H]+ calcd for C15H21O3+ 249.1485, found 249.1481; HRMS (ESI) m/z
[M + Na]+ calcd for C15H20NaO3+ 271.1305, found 271.1292.
Ethyl 2-Isopropyl-4-oxo-4-phenylbutanoate (4g):17 pale yellow
oil; Rf = 0.40 (ethyl acetate/petroleum ether = 1:15) (0.6 mmol scale,
44.6 mg, 30% yield) ATR-FTIR (cm−1) 2963, 1724, 1685, 1173, 756,
690, 560; 1H NMR (400 MHz, CDCl3) δ 7.99−7.96 (m, 2H), 7.58−
7.54 (m, 1H), 7.48−7.44 (m, 2H), 4.21−4.09 (m, 2H), 3.54−3.46 (m,
1H), 3.01−2.91 (m, 2H), 2.11−2.02 (m, 1H), 1.25 (t, J = 7.2 Hz, 3H),
0.99 (d, J = 7.0 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 198.8,
174.8, 136.8, 133.1, 128.5, 128.0, 60.4, 46.5, 37.3, 30.1, 20.2, 19.9, 14.2.
Ethyl 2-(1-Oxo-1,2,3,4-tetrahydronaphthalen-2-yl)propanoate
(4h): pale yellow oil; Rf = 0.35 (ethyl acetate/petroleum ether =
1:15) (0.6 mmol scale, 104.2 mg, 71% yield; dr = 1.2:0.8) ATR-FTIR
(cm−1) 2979, 2938, 1727, 1680, 1599, 1455, 1184, 741; 1H NMR (400
MHz, CDCl3) δ 8.02−8.00 (m, 1H), 7.48−7.43 (m, 1H), 7.31−7.27
(m, 1H), 7.24−7.22 (m, 1H), 4.18 (qd, J = 7.2 Hz, 1.0 Hz, 1.2H), 4.11
(q, J = 7.2 Hz, 0.8H), 3.21−2.96 (m, 3.6H), 2.90−2.85 (m, 0.4H),
2.20−2.05 (m, 1.4H), 1.98−1.87 (m, 0.6H), 1.30−1.24 (m, 3H), 1.20−
1.15 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 198.1, 197.9, 176.1,
174.6, 143.9, 143.7, 133.3, 133.2, 132.5, 132.3, 128.6, 128.5, 127.4,
126.6, 126.5, 60.5, 60.4, 50.5, 50.2, 39.2, 38.7, 29.3, 29.0, 25.8, 25.2,
+
14.2, 14.1, 13.3, 13.1; HRMS (ESI) m/z [M + H]+ calcd for C15H19O3
247.1329, found 247.1329; HRMS (ESI) m/z [M + Na]+ calcd for
C15H18NaO3+ 269.1148, found 269.1142.
4,4-Dimethyl-6-phenyl-4,5-dihydropyridazin-3(2H)-one (5a):12
white solid; Rf = 0.30 (ethyl acetate/petroleum ether = 1:5) (1.0
mmol scale, 136.0 mg, 67% yield); mp 144−146 °C; ATR-FTIR
(cm−1) 3213, 3093, 2919, 1657, 1612, 1341, 1241, 763, 694, 578; 1H
NMR (400 MHz, CDCl3) δ 8.60 (br, s, 1H), 7.73−7.70 (m, 2H), 7.44−
7.40 (m, 3H), 2.81 (s, 2H), 1.25 (s, 6H); 13C{1H} NMR (100 MHz,
CDCl3) δ 173.3, 150.8, 136.0, 129.8, 128.6, 125.8, 37.1, 34.0, 23.9.
4,4-Dimethyl-6-(p-tolyl)-4,5-dihydropyridazin-3(2H)-one (5b):
white solid; Rf = 0.30 (ethyl acetate/petroleum ether = 1:5) (1.0
mmol scale, 138.0 mg, 64% yield); mp 142−146 °C; ATR-FTIR
(cm−1) 3208, 3093, 2922, 1658, 1613, 1332, 1238, 809, 657, 562; 1H
NMR (400 MHz, CDCl3) δ 8.52 (br, s, 1H), 7.62−7.60 (m, 2H), 7.24−
(R)-4,4-Dimethyl-6-(4-(3-(2-methylpyrrolidin-1-yl)propoxy)-
phenyl)-4,5-dihydropyridazin-3(2H)-one (6e):3a white solid; Rf = 0.40
(MeOH/DCM = 1:10) (0.7 mmol scale, 194.7 mg, 81% yield); mp
117−121 °C; ATR-FTIR (cm−1) 3202, 3094, 2959, 2919, 1664, 1606,
1510, 1331, 1247, 1175, 830, 573, 550; 1H NMR (400 MHz, CDCl3) δ
8.59 (br, s, 1H), 7.66−7.64 (m, 2H), 6.93−6.91 (m, 2H), 4.09−4.04
(m, 2H), 3.25−3.20 (m, 1H), 3.05−2.98 (m, 1H), 2.75 (s, 2H), 2.40−
H
J. Org. Chem. XXXX, XXX, XXX−XXX