The Journal of Organic Chemistry
NOTE
and the mixture was stirred at room temperature for 16 h (an O2 balloon
may be fixed to the septum, if required). The solvent was evaporated
under vacuum, and the residue was dissolved in EtOAc (100 mL). The
solution was washed with saturated Na2CO3 (2 ꢁ 15 mL) and brine
(10 mL). The organic layer was dried over MgSO4, filtered, and concentrated
under vacuum. The resulting solids were purified by column chromatography
to yield the product as a white solid.
General Procedure for the Hydrogenation Reaction. Pd/C
(5 wt %, 0.075 mmol, 159 mg) was placed in a 20 mL two-neck round-
bottomed flask to which a solution of the alkene substrate (0.75 mmol)
in EtOH (7.5 mL) was added. H2 was passed through the mixture for
10 min, before it was left to stir under a H2 atmosphere for 4 h. Catalyst
was removed from the reaction mixture by filtering through a short silica
gel pad, which was rinsed with a little EtOH. The filtrate was evaporated
to furnish the product.
Data for (E)-3-(2-(acetylamino)phenyl)propenoic acid
butyl ester (2a): yield 160 mg, 82% as a white solid; mp 81ꢀ82 °C
(lit.8 mp 86 °C); Rf = 0.3, hexane/EtOAc (2/3); υmax/cmꢀ1 3258, 1710,
1665, 1633, 1527, 1264, 1171, 760; δH 7.82 (d, J = 15.9, 1H), 7.67ꢀ7.65
(m, 1H), 7.55ꢀ7.53 (m, 1H), 7.52 (br s, 1H),7.37ꢀ7.34 (m, 1H),
7.20ꢀ7.17 (m, 1H), 6.39 (d, J = 15.9, 1H), 4.18 (t, J = 6.6, 2H), 2.21 (s,
3H), 1.71ꢀ1.64 (m, 2H), 1.47ꢀ1.38 (m, 2H), 0.95 (t, J = 7.4, 3H); δC
169.3, 166.9, 139.6, 136.0, 130.7, 127.9, 126.9, 125.9, 125.6, 120.1, 64.6,
30.7, 23.9, 19.2, 13.7; m/z (EI) 261 (M+, 43), 219 (32), 146 (100), 118
(91), 43 (39).
Data for (E)-butyl 3-(2-acetamido-5-methylphenyl)acrylate
(2b): yield 178 mg, 86% as a white solid; mp 93ꢀ94 °C (lit.25 mp 97 °C);
Rf = 0.25, hexane/EtOAc (1/1); υmax/cmꢀ1 3240, 1710, 1663, 1634, 1520,
1264; δH (400 MHz, CDCl3) 7.78 (d, J = 15.8, 1H), 7.58 (br s, 1H), 7.51
(d, J = 8.3, 1H), 7.34 (d, J = 2.2, 1H), 7.16 (dd, J = 8.3, 2.2, 1H), 6.37 (d, J =
15.8, 1H), 4.16 (t, J = 6.7, 2H), 2.31 (s, 3H), 2.18 (s, 3H), 1.70ꢀ1.63 (m,
2H), 1.44ꢀ1.38 (m, 2H), 0.94 (t, J = 7.4, 3H); δC 169.2, 167.0, 139.6,
135.8, 133.5, 131.6, 128.0, 127.3, 125.8, 119.9, 64.6, 30.7, 23.9, 21.0, 19.2,
13.7; m/z (EI) 275 (M+, 42), 233 (23), 160 (100), 132 (78).
Data for (E)-butyl 3-(2-acetamido-5-methoxyphenyl)acrylate
(2c): yield 163 mg, 75% as a white solid; mp 129ꢀ130 °C (lit.8 mp
128ꢀ129 °C); Rf = 0.25, CHCl3; υmax/cmꢀ1 3256, 1707, 1651, 1639, 1529,
1242, 980, 729; δH 7.78 (d, J = 15.9, 1H), 7.45 (d, J = 8.8, 1H), 7.44 (br
s, 1H), 7.05 (d, J = 2.8, 1H), 6.93 (dd, J= 8.8, 2.8, 1H), 6.39 (d, J = 15.9, 1H),
4.20 (t, J = 6.7, 2H), 3.82 (s, 3H), 2.20 (s, 3H), 1.72ꢀ1.65 (m, 2H),
1.48ꢀ1.39 (m, 2H), 0.97 (t, J=7.4,3H);δC 169.7, 166.9, 157.7, 139.6, 130.2,
129.1, 128.0, 120.0, 116.4, 111.0, 64.6, 55.6, 30.7, 23.6, 19.2, 13.7; m/z (EI)
291 (M+, 9), 165 (78), 123 (76), 108 (100), 84 (57).
Data for (E)-butyl 3-(2-acetamido-5-chlorophenyl)acrylate
(2d): yield 72.6 mg, 32% as a white solid; mp 137ꢀ138 °C (lit.25 mp
140ꢀ141 °C); Rf = 0.55, hexane/EtOAc (3/1); υmax/cmꢀ1 3261, 1713,
1663, 1519, 1315, 1175; δH 8.03 (br s, 1H), 7.67 (d, J = 15.8, 1H), 7.54
(d, J = 8.7, 1H), 7.44 (d, J = 1.7, 1H), 7.22 (d, J = 8.7, 1.7, 1H), 6.32 (d, J =
15.8, 1H), 4.14 (t, J = 6.1, 2H), 2.15 (s, 3H), 1.66ꢀ1.60 (m, 2H),
1.42ꢀ1.36 (m, 2H), 0.93 (t, J = 7.4, 3H); δC 169.3, 166.6, 138.1, 134.5,
131.3, 130.4, 129.3, 126.8, 126.6, 121.3, 64.7, 30.6, 23.9, 19.2, 13.7; m/z (EI)
295 (M+, 48), 253 (47), 180 (100), 152 (54), 43 (51).
Data for (2E,20E)-dibutyl 3,30-(2-acetamido-1,3-phenyle-
ne)diacrylate (3a): yield 18 mg, 7% as a white solid; mp 141ꢀ142 °C;
Rf = 0.5, hexane/EtOAc (2/3); υmax/cmꢀ1 3248, 1716, 1665, 1635,
1279, 1172; δH 7.77 (d, J = 15.9, 2H), 7.67 (d, J = 7.8, 2H), 7.36 (t, J =
7.8, 1H), 7.22 (br s, 1H), 6.42 (d, J = 15.9, 2H), 4.19 (t, J = 6.6, 4H), 2.29
(s, 3H), 1.72ꢀ1.6 (m, 4H), 1.49ꢀ1.39 (m, 4H), 0.96 (t, J = 7.4, 6H); δC
169.6, 166.7, 139.5, 134.6, 133.2, 128.5, 128.1, 121.0, 64.6, 30.7, 23.2,
19.2, 13.7; m/z (EI) 387 (M+, 5), 272 (18), 91 (48), 198 (39), 170
(100); HRMS m/z (EI) calcd for C22H29NO5 (M+) 387.2046, found
387.2046. Anal. Calcd for C22H29NO5: C, 68.20; H, 7.54; N, 3.61.
Found: C, 68.29; H, 7.69; N, 3.66.
Data for (2E,20E)-Dibutyl 3,30-(2-acetamido-5-methyl-1,3-
phenylene)diacrylate (3b): yield 18 mg, 7% as a white solid; mp
122ꢀ123 °C; Rf = 0.4, hexane/EtOAc (1/1); υmax/cmꢀ1 3261, 1710,
1659, 1637, 1458, 1283, 1177, 981; δH (400 MHz, CDCl3) 7.74 (d, J =
16.0, 2H), 7.49 (s, 2H), 7.06 (br s, 1H), 6.43 (d, J = 16.0, 2H), 4.19 (t, J =
6.7, 4H), 2.38 (s, 3H), 2.28 (s, 3H), 1.72ꢀ1.66 (m, 4H), 1.46ꢀ1.38 (m,
4H), 0.96 (d, J = 7.4, 6H); δC 169.9, 166.8, 139.7, 137.7, 132.9, 132.4,
129.1, 120.5, 64.6, 30.7, 23.1, 21.1, 19.2, 13.7; m/z (EI) 401 (M+, 34),
358 (35), 286 (61), 212 (63), 184 (100), 57 (36); HRMS m/z (EI) calcd
for C23H31NO5 (M+) 401.2202, found 401.2201. Anal. Calcd for
C23H31NO5: C, 68.80;H, 7.78; N, 3.49. Found:C, 68.88; H, 7.69; N, 3.53.
Data for butyl 3-(2-acetamido-3,6-dimethoxyphenyl)pro-
panoate (4): yield 87 mg, 36% as a white solid; mp 91ꢀ92 °C; Rf = 0.4,
hexane/EtOAc (1/3); υmax/cmꢀ1 3254, 1729, 1660, 1486, 1256, 1082;
δH 7.85 (br s, 1H), 6.76ꢀ6.72 (m, 2H), 4.01 (t, J = 6.7, 2H), 3.78
(s, 3H), 3.78 (s, 6H), 2.86 (t, J = 6.7, 2H), 2.66 (t, J = 6.7, 2H), 2.22
(s, 3H), 1.57ꢀ1.51 (m, 2H), 1.36ꢀ1.29 (m, 2H), 0.89 (t, J = 7.4, 3H);
δC 174.9, 169.4, 151.9, 149.2, 127.3, 125.6, 109.7, 108.9, 64.5, 56.3, 55.7,
33.1, 30.6, 23.4, 21.1, 19.1, 13.7. m/z (EI) 323 (M+, 68), 281 (46), 207
(73), 192 (100); HRMS m/z (EI) calcd for C17H25NO5 (M+) 323.1733,
found 323.1733. Anal. Calcd for C17H25NO5: C, 63.14; H, 7.79; N, 4.33.
Found: C, 63.16; H, 7.79; N, 4.28.
Data for butyl 3-(4-acetamido-2,5-dimethoxyphenyl)pro-
panoate (5): yield 16 mg, 5% as a white solid; mp 94ꢀ95 °C; Rf = 0.6,
hexane/EtOAc (1/3); υmax/cmꢀ1 3325, 1730, 1678, 1526, 1216; δH
8.07 (s, 1H), 7.71 (br s, 1H), 6.70 (s, 1H), 4.06 (t, J = 6.7, 2H), 3.82
(s, 3H), 3.80 (s, 3H), 2.86 (t, J = 6.7, 2H), 2.57 (t, J = 6.7, 2H), 2.19
(s, 3H), 1.63ꢀ1.56 (m, 2H, overlapped with water peak), 1.36ꢀ1.31
(m, 2H), 0.91 (t, J = 7.4, 3H); δC 173.5, 168.1, 151.4, 141.2, 126.5, 122.4,
112.3, 103.6, 64.2, 56.3, 55.9, 34.4, 30.5, 26.1, 24.9, 19.1, 13.7; m/z (EI)
323 (M+, 100), 266 (55), 208 (80), 166 (79); HRMS m/z (EI) calcd for
C17H25NO5 (M+) 323.1733, found 323.1736. Anal. Calcd for
C17H25NO5: C, 63.14;H, 7.79; N, 4.33. Found:C, 63.17; H, 7.72; N, 4.43.
Data for methyl 3-(2-acetamidophenyl)-2-methylpro-
panoate (6a): yield 76 mg, 43% over two steps, as a white solid; mp
79ꢀ80 °C; Rf = 0.1, hexane/EtOAc (1/1); υmax/cmꢀ1 3263, 1733,
1662, 1525, 1451, 753; δH 8.49 (br s, 1H), 7.76ꢀ7.74 (m, 1H),
7.26ꢀ7.22 (m, 1H), 7.18ꢀ7.16 (m, 1H), 7.13ꢀ7.08 (m, 1H), 3.62
(s, 3H), 3.01 (dd, J = 9.6, 14.1, 1H), 2.80ꢀ2.74 (m, 1H), 2.57 (dd, J =
4.5, 14.1, 1H), 2.23 (s, 3H), 1.32 (d, J = 7.2, 3H); δC 178.2, 168.8, 135.5,
131.2, 130.4, 127.2, 125.2, 124.7, 52.2, 41.8, 34.4, 24.3, 18.6; m/z (EI)
235 (M+, 43), 162 (29), 132 (34), 106 (100). HRMS m/z (EI) calcd
for C13H17NO3 (M+) 235.1208, found 235.1205. Anal. Calcd for
C13H17NO3: C, 66.36;H, 7.28; N, 5.95. Found:C, 66.44; H, 7.34; N, 5.90.
Data for methyl 3-(2-acetamido-5-methylphenyl)-2-methyl-
propanoate (6b): yield 106.5 mg, 57% over two steps, as a white solid;
mp 91ꢀ92 °C; Rf = 0.3, CH2Cl2/EtOAc (1/2); υmax/cmꢀ1 3265, 1733,
1659, 1520, 1168; δH 8.37 (br s, 1H), 7.58 (d, J = 8.2, 1H), 7.03 (dd, J =
8.2, 2.3, 1H), 6.95 (d, J = 2.3, 1H), 3.62 (s, 3H), 2.98 (dd, J = 14.1, 9.8,
1H), 2.80ꢀ2.73 (m, 1H), 2.53 (dd, J = 14.1, 4.4, 1H), 2.28 (s, 3H), 2.22
(s, 3H), 1.32 (d, J = 7.1, 3H); δC 178.2, 168.8, 134.8, 132.8, 131.3, 130.8,
127.8, 124.9, 52.1, 41.8, 34.4, 21.2, 20.8, 18.6; m/z (EI) 249 (M+, 52),
175 (70), 146 (43), 120 (100); HRMS m/z (EI) calcd for C14H19NO3
(M+) 249.1365, found 249.1366. Anal. Calcd for C14H19NO3: C, 67.45;
H, 7.68; N, 5.62. Found: C, 67.47; H, 7.70; N, 5.58.
Data for methyl 3-(2-acetamido-5-methoxyphenyl)-2-
methylpropanoate (6c): yield 91 mg, 46% over two steps, as a
white solid; mp 92.5ꢀ93.5 °C; Rf = 0.08, hexane/EtOAc (1/1); υmax
/
cmꢀ1 3255, 1736, 1657, 1502, 1230; δH 8.19 (br s, 1H), 7.52 (d, J = 8.8,
1H), 6.77 (dd, J = 8.8, 2.9, 1H), 6.68 (d, J = 2.9, 1H), 3.77 (s, 3H), 3.62
(s, 3H), 2.98 (dd, J = 14.0, 9.7, 1H), 2.79ꢀ2.74 (m, 1H), 2.51 (dd, J =
14.0, 4.7, 1H), 2.21 (s, 3H), 1.31 (d, J = 7.2, 3H); δC 178.0, 169.0, 157.1,
133.7, 128.5, 126.9, 115.6, 112.3, 55.4, 52.1, 41.7, 34.6, 24.0, 18.6; m/z
(EI) 265 (M+, 89), 233 (44), 192 (36), 136 (100); HRMS m/z (EI)
8025
dx.doi.org/10.1021/jo201164m |J. Org. Chem. 2011, 76, 8022–8026