反应详情

A magnetically stirred solution of 0.848 gram of N-(2-amino-5-iodobenzoyl)-β-alanine ethyl ester (2.0 mmol), 0.35 mL 2,6-lutidine (3.0 mmol), 0.19 mL methyl iodide (3.0 mmol), and 15 mL dimethylformamide was heated to 50° C. for 15 hours. The reaction mixture was allowed to cool to room temperature and concentrated in vacuo. The resulting residue was disolved in 75 mL ethyl acetate and washed 1×50 mL 10% citric acid, 1×50 mL sat. sodium bicarbonate, 1×50 mL brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting oil was further purified by column chromatography, using silica gel, eluting with a solvent gradient of 35/65 ethyl acetate/hexane to 65/35 ethyl acetate/hexane (TLC, SiO2, 1:1 EtOAc/hexane, Rf =0.84, υv positive) to yield 305 mgs (35%) of N-(2-methylamino-5-iodobenzoyl)-β-alanine benzyl ester. 1H NMR (CDCl3, dTMS) 7.56 (2H, m, Ar--H o,p--CON), 7.43 (1H, bq, 3JHH =5 Hz, NHMe), 7.38-7.32 (5H, s, ArH Ph), 6.62 (1H, bt, 3JHH =6 Hz, CONH), 6.42 (1H, d, 3JHH =9 Hz, Ar--H m--CON), 5.16 (2H, s, OCH2), 3.64 (2H, q, 3JHH =6 Hz, NCH2), 2.81 (3H, d, 3JHH =5 Hz, NCH3), 2.64 (2H, t, 3JHH =6 Hz, CH2CO2). 13C NMR (CDCl3, δTMS) 172.4, 168.4, 148.8, 141.0, 135.5, 128.7, 128.4, 128.3, 117.3, 113.4, 74.1, 66.7, 35.2, 34.0, 29.6.

1. concentrationconcentrated in vacuo
2. washwashed 1×50 mL 10% citric acid, 1×50 mL sat. sodium bicarbonate, 1×50 mL brine
3. dry with materialdried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe resulting oil was further purified by column chromatography
7. washeluting with a solvent gradient of 35/65 ethyl acetate/hexane to 65/35 ethyl acetate/hexane (TLC, SiO2, 1:1 EtOAc/hexane, Rf =0.84, υv positive)