反应详情

温度

-10 °C

To a solution containing 0.80 g (3.5 mmol) of 4-methanesulfonamido-phenylacetic acid (Example 32) in 20 ml of N,N-dimethylformamide (DMF) 0.46 ml (0.42 g, 4,2 mmol) of 4-methylmorpholine is added, the mixture is cooled to −10° C. and 0.65 ml (0.70 g, 5 mmol) of isobutyl chloroformate is added. After 10 minutes a solution containing 0.68 g (3.5 mmol) of N-methyl-2-(2,3-dimethylphenoxy)-1-methylethylamine (Example 44) in 3 ml of DMF pre-cooled to −10° C. is added, then the pH value of the mixture is adjusted to 8.5 by adding triethylamine. The reaction mixture is stirred at −10° C. for 1 hour, then at 0° C. for 1 hour. Then, the solvent is evaporated under reduced pressure and the solid residue is alkalinized by adding aqueous ammonia solution and distributed between water and ethyl acetate. The aqueous phase is washed twice with ethyl acetate, the combined organic phase is washed once with water, dried over sodium sulphate and evaporated. Thus, 1.13 g of the title substance are obtained as an amorphous substance, which is suitable to the next step without further purification. Yield: 80%.

1. additionis added
2. temperaturepre-cooled to −10° C.
3. additionis added
4. waitat 0° C. for 1 hour
5. customThen, the solvent is evaporated under reduced pressure
6. additionby adding aqueous ammonia solution
7. washThe aqueous phase is washed twice with ethyl acetate
8. washthe combined organic phase is washed once with water
9. dry with materialdried over sodium sulphate
10. customevaporated
11. customThus, 1.13 g of the title substance are obtained as an amorphous substance, which
12. customis suitable to the next step without further purification