반응 #421512

반응 방정식

methyl 1-amino-4-bromo-2-naphthoate hydrobromide

4-methoxybenzylzinc chloride

→

Methyl 1-amino-4-bromo-2-naphthoate hydrobromide

methyl 1-amino-4-(4-methoxybenzyl)-2-naphthoate

용매

ethyl acetate

water

반응 조건

후처리

1. 1
   온도cooled to rt
2. 2
   기타The mixture was partitioned
3. 3
   추출the organic extract
4. 4
   세척was washed with brine
5. 5
   건조dried over sodium sulfate
6. 6
   여과filtered
7. 7
   농축concentrated in vacuo
8. 8
   기타The residue was purified via silica gel chromatography
9. 9
   세척eluting with 0-20% ethyl acetate in hexanes

실험 절차

Methyl 1-amino-4-bromo-2-naphthoate hydrobromide was prepared as described in Example 1. To a round bottom flask containing methyl 1-amino-4-bromo-2-naphthoate hydrobromide (3.50 g, 9.69 mmol) under an atmosphere of nitrogen was added 4-methoxybenzylzinc chloride (97.0 mL, 0.5 M in THF, 48.5 mmol) and tetrakis(triphenylphosphine)palladium(0) (10 mol %). The mixture was heated at 90° C. for 7 h, cooled to rt, and diluted with 50 mL of ethyl acetate and 50 mL of water. The mixture was partitioned and the organic extract was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-20% ethyl acetate in hexanes, to provide methyl 1-amino-4-(4-methoxybenzyl)-2-naphthoate that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 322.0 for [M+H]+. A solution of the above prepared compound (1.41 g, 4.39 mmol) in N,N-dimethylformamide dimethylacetal (1.76 mL, 13.2 mmol) was heated at 100° C. for 4 h. Additional N,N-dimethylformamide dimethylacetal (0.44 mL, 3.3 mmol) was added and the solution was heated at 100° C. for 1 h. The mixture was cooled to rt, concentrated in vacuo to provide methyl 1-{[(1E)-(dimethylamino)methylene]amino}-4-(4-methoxybenzyl)-2-naphthoate that gave a mass ion (ES+) of 377.0 for [M+H]+. To a solution of the above prepared compound (0.040 g, 1.1 mmol) in 0.5 mL of acetic acid was added 3-amino-5-methylpyrazole (10.7 mg, 1.10 mmol). The mixture was heated at 100° C. for 6 h and then cooled to rt and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC to provide the title compound that gave a mass ion (ES+) of 433.1653 for [M+H]+.

출처