91% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18h; |
1 Example 1: Methyl 4-(4-formyl-2-methoxvnhenoxv)butanoate (i)
A mixture of vanillin (20.0 g, 131 mmol), methyl 4-bromobutanoate (17.5 mL, 139mmol) and potassium carbonate (27.2 g, 197 mmol) in N,N-dimethylformamide (100mL) was stirred at room temperature for 18 h. The reaction mixture was diluted with water (soo mL) and the title compound (30.2 g, 91%) was obtained by filtration as a white solid. The product was carried through to the next step without any further purification.1H NMR (400 MHz, CDC13) 6 9.84 (s, 1H), 7.46-7.37 (m, 2H), 6.98 (d, J=8.2 Hz, 1H),4.16 (t, J=6.3 Hz, 2H), 3.91 (s, 3H), 3.69 (s, 3H), 2.56 (t, J=7.2 Hz, 2H), 2.20 (quin, J=6.7 Hz, 2H); 13C NMR (ioo MHz, CDC13) 6 190.9, 173.4, 153.8, 149.9, 130.1, 126.8, 111.6, 109.2, 67.8, 6.o, 51.7, 30.3, 24.2; MS m/z (ElMS) = 271.9 (M+Na) LCMS (Method A): tR = 6.48 mm. |
91% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18h; |
2 methyl 4-(4-formyl-2-methoxyphenoxy)butanoate (1)
A mixture of vanillin (20.0 g, 131 mmol), methyl 4-bromobutanoate (17.5 mL, 139 mmol) and potassium carbonate (27.2 g, 197 mmol) in A V-dimethylformamide (100 mL) was stirred at room temperature for 18 h. The reaction mixture was diluted with water (500 mL) and the title compound (30.2 g, 91%) was obtained by filtration as a white solid. The product was carried through to the next step without any further purification. (1374) NMR (400 MHz, CDCI3) δ 9.84 (s, lH), 7-46-7-37 (m, 2H), 6.98 (d, J=8.2 Hz, lH), 4.16 (t, J=6.3 Hz, 2H), 3.91 (s, 3H), 3.69 (s, 3H), 2.56 (t, J=7.2 Hz, 2H), 2.20 (quin, J=6.7 Hz, 2H); FontWeight="Bold" FontSize="10" C NMR (100 MHz, CDC13) δ 190.9, 173.4, 153-8, 149-9, 130-1, 126.8, 111.6, 109.2, 67.8, 56.0, 51.7, 30.3, 24.2; MS M/Z (EIMS) = 271.9 (M+Na)+, 253 (M+H)+; LCMS (Method A): tR = 6.48 min. |
91% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18h; |
Methyl 4-(4-formyl-2-methoxyphenoxy)butanoate (l)
A mixture of vanillin (20.0 g, 131 mmol), methyl 4-bromobutanoate (17.5 mL, 139 mmol) and potassium carbonate (27.2 g, 197 mmol) in N,iV-dimethylformamide (too mL) was stirred at room temperature for 18 h. The reaction mixture was diluted with water (500 mL) and the title compound (30.2 g, 91%) was obtained by filtration as a white solid. The product was carried through to the next step without any further purification. NMR (400 MHz, CDCl3) <59.84 (s, lH), 7.46-7.37 (m, 2H), 6.98 (d, J=8.2 HZ, lH), 4.16 (t, J=6.3 HZ, 2H), 3.91 (s, 3H), 3.69 (s, 3H), 2.56 (t, J=7- 2 Hz, 2H), 2.20 (quin, J= 6.7 Hz, 2H); C NMR (too MHz, CDCl3) d 190.9, 173.4, 153-8, 149-9, 130.1, 126.8, 111.6, 109.2, 67.8, 56.0, 51.7, 30.3, 24.2; MS m/z (EIMS) = 271.9 (M+Na)+; MS (ES+): m/z = 253 (M+H)+; LCMS (Method A): £R = 6.48 min. |
91% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18h; |
Methyl 4-(4-formyl-2-methoxyphenoxy)butanoate (1)
A mixture of vanillin (20.0 g, 131 mmol), methyl 4-bromobutanoate (17.5 mL, 139 mmol) and potassium carbonate (27.2 g, 197 mmol) in N,N-dimethyl-formamide (100 mL) was stirred at room temperature for 18 h. The reaction mixture was diluted with water (500 mL) and the title compound (30.2 g, 91%) was obtained by filtration as a white solid. The product was carried through to the next step without any further purification. 1H NMR (400 MHz, CDC13) δ 9.84 (s, lH), 7.46-7.37 (m, 2H), 6.98 (d,•J=8.2 Hz, lH), 4.16 (t, J=6.3 HZ, 2H), 3.91 (s, 3H), 3.69 (s, 3H), 2.56 (t, J=7.2 Hz, 2H), 2.20 (quin, J= 6.7 Hz, 2H); 13C NMR (100 MHz, CDCI3) δ 190.9, 173.4, 153-8, 149.9, 130.1, 126.8, 111.6, 109.2, 67.8, 56.0, 51.7, 30.3, 24.2; MS (ES+): m/z = 253 (M+H)+; LCMS (Method A): tR= 6.48 min. |
91% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18h; |
Methyl 4-(4-formyl-2-methoxyphenoxy)butanoate (1)
A mixture of vanillin (20.0 g, 131 mmol), methyl 4-bromobutanoate (17.5 mL, 139 mmol) and potassium carbonate (27.2 g, 197 mmol) in N,N-dimethyl-formamide (100 mL) was stirred at room temperature for 18 h. The reaction mixture was diluted with water (500 mL) and the title compound (30.2 g, 91%) was obtained by filtration as a white solid. The product was carried through to the next step without any further purification. 1H NMR (400 MHz, CDC13) δ 9.84 (s, lH), 7.46-7.37 (m, 2H), 6.98 (d,•J=8.2 Hz, lH), 4.16 (t, J=6.3 HZ, 2H), 3.91 (s, 3H), 3.69 (s, 3H), 2.56 (t, J=7.2 Hz, 2H), 2.20 (quin, J= 6.7 Hz, 2H); 13C NMR (100 MHz, CDCI3) δ 190.9, 173.4, 153-8, 149.9, 130.1, 126.8, 111.6, 109.2, 67.8, 56.0, 51.7, 30.3, 24.2; MS (ES+): m/z = 253 (M+H)+; LCMS (Method A): tR= 6.48 min. |
88% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; |
|
88% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6h; |
|
85% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; |
|
85% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; |
1.viii.a
4-(4-Formyl-2-methoxy-phenoxy)-butyric acid methyl ester (11) A slurry of vanillin 10 (40 g, 0.262 mol), methyl-4-bromobutyrate (50 g, 34.2 mL, 1.05 eq) and potassium carbonate (54 g, 1.5 eq) in DMF (200 mL) was stirred at room temperature overnight (16 hours). A large volume of water was added (1 L) whilst stirring. The white precipitate was filtered, washed with water and dried to yield 40, 6Og (85%). mp 73°C. 1H NMR (CDCI3) δ 9.80 (1H, s) 7.43 (2H, m), 6.97 (1H, d, J = 8.1 Hz), 4.16 (2H, t, J = 6.28 Hz), 3.92 (3H, s), 3.70 (3H, s), 2.57 (2H, t, J = 7.15 Hz), 2.20 (2H, p, J = 6.71 Hz); 13C NMR (CDCI3) 5 190.9, 173.4, 153.8, 149.9, 130.1, 126.8, 111.5, 109.2, 67.8, 56.0, 51.7, 30.3, 24.2; IR (golden gate) vmax 1728, 1678, 1582, 1508, 1469, 1426, EPO 1398, 1262, 1174, 1133, 1015, 880, 809, 730 cm"1; MS (ES+) m/z (relative intensity) 253 ([M + H]+-, 100). |
85% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6h; |
|
85% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6h; |
Synthesis of methyl 4-(4-formyl-2-methoxyphenoxy)butanoate (2.4)
A suspension of 2.3 (20 g, 131 mmol), methyl 4-bromobutanoate (24.986 g, 1.05 equiv.) and potassium carbonate (27.25 g, 1.5 equiv.) was prepared in DMF (too ml) and stirred at room temperature for six hours. After completion of reaction was confirmed by LC-MS analysis, the reaction mixture was diluted with water (500 ml). A white precipitate formed. This precipitate was filtered and washed with cold water to yield a white solid product which was dried in a vacuum oven at 40 °C to yield 28.1 g of 2.4 (85% yield). |
66% |
With potassium carbonate In DMF (N,N-dimethyl-formamide) for 16h; |
iii
(III) 4- (4-HYDROXYMETHYL-2-METHOXY-5-NITROPHENOXY) butyric acid allyl ester (52) 50 51 52 4- 4-FORMYL-2-METHOXYPHENOXY)-BUTYRIC ACID methyl ester (48); A solution of vanillin (47) (40.00 g, 262.89 mmol) and methyl-4- bromobutyrate (50.00 g, 276.18 mmol) in DMF (200 ML) was allowed to stir over potassium carbonate (51.53 g, 372.40 mmol) for 16 hours. Water was added to the reaction mixture at which time the product crystallised. The resulting mixture was filtered and dried in vacuo for 16 hours to afford the keto-ester (48) as a white solid (41.3g, 66%). MP = 57-59°C. 1H NMR (250 MHz, CDCLG) 6 9.80 (s, 1H), 7.46-7. 40 (m, 2H), 6.97 (d, J = 8.1 Hz, 1H), 4.16 (t, J = 6.3 Hz, 2H), 3.92 (s, 3H), 3.70 (s, 3H), 2.57 (t, J = 7.2 Hz, 2H), 2.20 (pent, J = 6.7 Hz, 2H). 13C NMR (67.8 MHz, CDC13) 188.2 (C1), 173.7 (C12), 153.8 (Cquat. ), 152.0 (Cquat. ), 144.1 (Cquat. ), 125.8 (CMETHINE), 110.3 (C3), 108.5 (C6), 69.0 (C9), 57.0 (C8), 52.2 (C13), 30.6 (CLL), 24.5 (C10). It was decided to adopt the numbering system shown in the figure below for the molecule for ease of peak assignment IN 13C NMR. IR (cm-1) 3450,3332, 2952,1737, 1685,1587, 1467,1407, 1006, 938,864, 813,730, 656. MS (M+) 253. Anal. Calcd for C13 H16 Os : C, 61.90 ; H, 6.39. Found: C, 61.50 ; H, 6.39. |
60% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6h; |
|
|
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 1.5h; |
|