反应详情

Methanol (1.54 ml, 0.0381 mole) was added to a suspension of sodium (0.876 g, 0.0381 mole) in dry tetrahydrofuran and the mixture stirred for 30 minutes. A solution of N-formyl-N-(3,5-difluorobenzyl)-glycine methyl ester (8.50 g, 0.0349 mole) in methyl formate (6.57 ml, 0.107 mole) was added dropwise with cooling at 10° to 15° C. and the resulting mixture was stirred overnight at room temperature. The solvent was removed under vacuum and the residue was diluted with 100 ml water-methanol (1:1). The solution was treated with activated carbon, filtered, and cooled in ice. Hydrochloric acid (12N, 6.4 ml) and a solution of potassium thiocyanate (4.25 g, 0.0437 mole) in a minimum amount of water were added and the resulting solution was heated at 65°-70° C. for 24 hours. The solution was treated with activated carbon, filtered and the solvent was removed under vacuum until a precipitate formed. The mixture was cooled in ice and the product filtered and washed with a mixture of methanol-water. The product was trituarted with ethanol, filtered and dried to give a solid melting at 177°-178° C. (6.75 g, 68%).

1. temperaturewith cooling at 10° to 15° C.
2. stirringthe resulting mixture was stirred overnight at room temperature
3. customThe solvent was removed under vacuum
4. additionthe residue was diluted with 100 ml water-methanol (1:1)
5. additionThe solution was treated with activated carbon
6. filtrationfiltered
7. temperaturecooled in ice
8. temperaturethe resulting solution was heated at 65°-70° C. for 24 hours
9. additionThe solution was treated with activated carbon
10. filtrationfiltered
11. customthe solvent was removed under vacuum until a precipitate
12. customformed
13. temperatureThe mixture was cooled in ice
14. filtrationthe product filtered
15. washwashed with a mixture of methanol-water
16. filtrationfiltered
17. customdried