3-Methyl-2-nitrobenzoic acid → (1Z)-3-imino-3-(3-methyl-4-nitrophenyl)-1-[2-(propyloxy)phenyl]prop-1-en-1-amine

A solution of 1,1,1-trimethyl-N-(trimethylsilyl)silanamine (2.70 g, 16.8 mmol) in dry tetrahydrofuran (40 mL) was cooled to −78° C., at which time was added n-butyllithium 1.6 N (10.5 mL, 16.8 mmol) followed by commercially available acetophenone (5.50 g, 31 mmol). The reaction mixture was stirred for 1 h at −78° C. to give the 1-[2-(propyloxy)phenyl]ethanone lithium salt. Concurrent with the above was prepared a solution of 1-[(3-methyl-4-nitrophenyl)carbonyl]-1H-imidazole by adding 1,1′-carbonylbis(1H-imidazole) (2.70 g, 16.8 mmol) to 3-methyl-2-nitrobenzoic acid (2.50 g, 14.0 mmol) in tetrahydrofuran (40 mL) at room temperature. To the 1-[2-(propyloxy)phenyl]ethanone lithium salt solution was slowly added the 1-[(3-methyl-4-nitrophenyl)carbonyl]-1H-imidazole solution at −78° C. and the mixture was allowed to warm to room temperature. The reaction mixture was quenched with hydrochloric acid 1.0 N (100 mL) and the product was extracted with ethyl acetate (150 mL). The organic phase was washed with brine (80 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chomatography (SiO2, ethyl acetate/hexanes 1:2), followed by re-crystallization from diethyl ether and hexanes (1:5) to afford (1Z)-3-imino-3-(3-methyl-4-nitrophenyl)-1-[2-(propyloxy)phenyl]prop-1-en-1-amine (2.20 g, 46%).

1. customThe reaction mixture was quenched with hydrochloric acid 1.0 N (100 mL)
2. extractionthe product was extracted with ethyl acetate (150 mL)
3. washThe organic phase was washed with brine (80 mL)
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash chomatography (SiO2, ethyl acetate/hexanes 1:2)
8. customfollowed by re-crystallization from diethyl ether and hexanes (1:5)

ORD record

ord-c7136c1339e7475783f0c97485affc18

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101625B2