3-[(E)-2-(Dimethylamino)ethenyl]-2-nitrobenzoic acid methyl ester synthesis

Yield:68109-89-7 88%

Reaction Conditions:

at 120; for 42 h;

Steps:

74

Example 74; Synthesis of (3S)-3-amino-1-hydroxy-8-(morpholin-4-ylmethyl)-3,4-dihydroquinolin-2(1H)-one, trifluoroacetic acid salt (104); Methyl 3-formyl-2-nitrobenzoate (98); N,N-Dimethylformamide dimethyl acetal (10 g, 84 mmol) and methyl 3-methyl-2-nitrobenzoate (8.0 g, 41 mmol) were combined and heated to 120° C. for 42 h. After cooling, the mixture was concentrated under reduced pressure to provide methyl 3-[(E)-2-(dimethylamino)vinyl]-2-nitrobenzoate (9.0 g, 88%), which was dissolved in a 1:1 mixture of water and THF. After addition of sodium periodate (99%, 23.3 g, 108 mmol), the reaction was allowed to stir for 18 h, then was filtered. The filtrate was washed with water and with saturated aqueous sodium chloride solution, then dried over sodium sulfate. Filtration and removal of solvent under reduced pressure provided a residue, which was purified using silica gel chromatography (Gradient: 0% to 80% EtOAc in heptane) to provide the product as a solid (2.2 g, 29%). ¹H NMR (500 MHz, CDCl₃) δ 3.96 (s, 3H), 7.78 (ddd, J=7.8, 7.8, 0.6 Hz, 1H), 8.19 (dd, J=7.8, 1.5 Hz, 1H), 8.29 (dd, J=7.8, 1.6 Hz, 1H), 9.99 (d, J=0.5 Hz, 1H).

References:

US2010/324043,2010,A1 Location in patent:Page/Page column 46-47