反应详情

To a solution of 5-(2-formyl-4-nitro-N-methylanilino)pentanoic acid (3.0 g) in DMF (8.1 ml), potassium carbonate (1.6 g) and a solution of methyl iodide/DMF (1.8 g/1 ml) were added at room temperature, and the resulting mixture was stirred further for 2 hours. To the mixture, dimethyl carbonate (18 ml) and subsequently a solution of 28% sodium methoxide in methanol (5.0 g) were added and the resulting mixture was stirred at 50° C. for 2.5 hours. The mixture was allowed to cool to room temperature, and neutralized with 1N hydrochloric acid. After ethyl acetate extraction, the organic layer was washed with saturated salt water, dried over anhydrous sodium sulfate, and concentrated. The concentrate was redissolved in hot isopropyl alcohol [IPA], and the solution was allowed to cool to room temperature, stirred at room temperature further for 1 hour, and at ice temperature for 0.5 hours. The precipitated crystal was collected by filtration, and washed with IPA. The crystal was purified by silica gel column chromatography (n-hexane/ethyl acetate=2/1 to 1/1), and subsequent concentration of the appropriate eluate gave yellow crystal of 8-nitro-1-methyl-1,2,3,4-tetrahydro-1-benzazocin-5-carboxylic acid methylester (2.3 g, yield 78%). mp. 127–129° C. 1H-NMR(CDCl3, δ, 300 MHz): 1.38–1.72(2H, m), 2.35–2.80(2H, m), 3.02(3H, s), 3.42–3.85(2H, m), 3.80(3H, s), 6.65(1H, d, J=9.4 Hz), 7.80(1H, s), 7.99–8.06(2H,m). Anal. Calcd for C14 H16 N2 O2: C,60.86; H,5.84; N,10.14. Found: C,60.79; H,5.81; N,9.98. IR (KBr, cm−1): 1708, 1255, 1191.

1. stirringthe resulting mixture was stirred at 50° C. for 2.5 hours
2. extractionAfter ethyl acetate extraction
3. washthe organic layer was washed with saturated salt water
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated
6. dissolutionThe concentrate was redissolved in hot isopropyl alcohol [IPA]
7. temperatureto cool to room temperature
8. stirringstirred at room temperature further for 1 hour
9. waitat ice temperature for 0.5 hours
10. filtrationThe precipitated crystal was collected by filtration
11. washwashed with IPA