# Trimethoxycinnamates and Their Cholinesterase Inhibitory Activity
## 2 Materials and Methods
### Synthesis  
General Procedure Used to Synthesize Esters **1-12**  
Trimethoxycinnamic acid (0.5 g, 0.2 mmol) was suspended in dry toluene (5 mL) at room temperature and thionyl chloride (0.25 mmol) was added dropwise. The reaction mixture was stirred for 1 h under reflux. The residue was used directly in the next step. Into the solution of trimethoxycinnamic acid chloride in dry toluene (5 mL), triethylamine (0.25 mmol) and corresponding substituted alcohol (0.2 mmol) were added dropwise. The mixture was stirred under reflux for 1 h, after which the solvent was removed under reduced pressure. The residue was extracted with EtOAc. Combined organic layers were washed with 1M HCl and distilled water and dried over anhydrous MgSO\({}_{4}\). The solvent was evaporated to dryness under reduced pressure. The crude product was recrystallized from EtOH. _Phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate_ **(1)**[14]. Yield 56%; Mp 105-107 \({}^{\circ}\)C; IR (ATR, cm\({}^{-1}\)): 3041, 3012, 2939, 2835, 1721, 1631, 1580, 1507, 1495, 1485, 1468, 1455, 1437, 1416, 1337, 1321, 1266, 1241, 1180, 1156, 1122, 1067, 1023, 999, 971, 931, 903, 868, 846, 833, 816, 785, 752, 724, 687, 940, 603, 553; \({}^{1}\)H-NMR (DMSO-\(d_{6}\)), \(\delta\): 7.82 (d, \(J\) = 15.8 Hz, 1H), 7.47-7.44 (m, 2H), 7.30-7.27 (m, 1H), 7.22-7.20 (m, 2H), 7.18 (s, 2H), 6.92 (d, \(J\) = 15.8 Hz, 1H), 3.84 (s, 6H), 3.72 (s, 3H); \({}^{13}\)C-NMR (DMSO-\(d_{6}\)), \(\delta\): 165.1, 153.1, 150.5, 146.7, 139.8, 129.5, 129.5, 125.8, 121.8, 116.4, 106.3, 60.1, 56.1; HR-MS: C\({}_{18}\)H\({}_{19}\)O\({}_{5}\) [M + H]\({}^{+}\) calculated 315.1227 _m/z_, found 315.1228 _m/z_. _4-Methoxyphenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate_ **(2)**. Yield 75%; Mp 131-133 \({}^{\circ}\)C; IR (ATR, cm\({}^{-1}\)) 3000, 2967, 2945, 2842, 1703, 1627, 1582, 1502, 1453, 1419, 1339, 1321, 1277, 1246, 1186, 1155, 1121, 1099, 1020, 1008, 992, 941, 925, 915, 883, 863, 840, 832, 818, 805, 792, 779, 701, 658, 640, 629, 607, 544, 521, 487, 447; \({}^{1}\)H-NMR (DMSO-\(d_{6}\)), \(\delta\): 7.78 (d, \(J\) = 15.8 Hz, 1H), 7.17 (s, 2H), 7.14-7.11 (m, 2H), 6.99-6.96 (m, 2H), 6.89 (d, \(J\) = 15.8 Hz, 1H), 3.83 (s, 6H), 3.77 (s, 3H), 3.71 (s, 3H); \({}^{13}\)C-NMR (DMSO-\(d_{6}\)), \(\delta\): 165.4, 156.8, 153.1, 146.4, 1439, 139.7, 129.5, 122.6, 116.5, 114.4, 106.2, 60.1, 56.1, 55.4; HR-MS: C\({}_{19}\)H\({}_{21}\)O\({}_{6}\) [M + H]\({}^{+}\) calculated 345.1333 _m/z_, found 345.1332 _m/z_. _4-Methylphenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate_ **(3)**. Yield 51%; Mp 103-105 \({}^{\circ}\)C; IR (ATR, cm\({}^{-1}\)): 2937, 2837, 1719, 1642, 1581, 1506, 1469, 1454, 1437, 1416, 1382, 1337, 1321, 1273, 1241, 1187, 1166, 1156, 1124, 1021, 998, 972, 939, 925, 917, 861, 829, 817, 808, 788, 774, 706, 632, 603, 528, 517, 501; \({}^{1}\)H-NMR (DMSO-\(d_{6}\)), \(\delta\): 7.79 (d, \(J\) = 15.8 Hz, 1H), 7.25-7.23 (m, 2H), 7.17 (s, 2H), 7.09-7.06 (m, 2H), 6.90 (d, \(J\) = 15.8 Hz, 1H), 3.83 (s, 6H), 3.77 (s, 3H), 3.23 (s, 3H); \({}^{13}\)C-NMR (DMSO-\(d_{6}\)), \(\delta\): 165.2, 153.1, 148.3, 146.5, 139.8, 134.9, 129.9, 129.5, 121.5, 116.5, 106.3, 60.1, 56.1, 20.4; HR-MS: C\({}_{19}\)H\({}_{21}\)O\({}_{5}\) [M + H]\({}^{+}\) calculated 329.1380 _m/z_. _4-Fluorphenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate_ **(4)**.