反应详情

A suspension of 0.200 g (0.64 mmol) 2-methoxy-4-methyl-6-(3-trifluoromethyl-phenyl)-nicotinic acid in 5 ml of CH2Cl2 was treated at RT with one drop of DMF; then, 0.06 ml=0.09 g (0.71 mmol) of oxalyl chloride was added to this solution drop by drop below 25° C. and the reaction mixture was stirred for 0.5 hour. After removal of the solvents by evaporation in a high vacuum, the residue was dissolved again in 10 ml of CH2Cl2 and 0.36 ml=0.26 g (2.57 mmol) of Et3N was added while stirring, followed by 0.099 g (0.64 mmol) of 4-pyrrolidin-1-yl-piperidine. The reaction mixture was stirred at RT. After 16 hours, it was poured into crashed ice and extracted twice with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 98:2 to 4:1) to give 0.278 g (97%) of the title compound as yellow amorphous solid. MS: 448.1 (MH+).

1. customAfter removal of the solvents
2. customby evaporation in a high vacuum
3. dissolutionthe residue was dissolved again in 10 ml of CH2Cl2
4. stirringwhile stirring
5. stirringThe reaction mixture was stirred at RT
6. waitAfter 16 hours
7. additionit was poured
8. extractionextracted twice with CH2Cl2
9. washthe organic phases were washed with water
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. customevaporated
13. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 98:2 to 4:1)