反应详情

To a stirred mixture of 2.78 grams (0.02 mole) of monomethyl methoxymalonate prepared in Example LVI (Compound 214) and 3.56 grams (0.02 mole) of 4-bromo-2-fluoroaniline in approximately 100 milliliters of dry tetrahydrofuran was fed dropwise a solution of 3.87 grams (0.02 mole) of 1,3-dicyclohexylcarbodiimide in about 30 milliliters of dry tetrahydrofuran, while cooling the reaction mixture in an ice-water bath. The reaction mixture was allowed to warm slowly to room temperature and stirring continued for an approximate 65-hour period. The precipitated 1,3-dicyclohexylurea by-product (3.15 grams) was removed by filtration and the filtrate vacuum evaporated and the residue dissolved in methylene chloride. The latter solution was extracted with dilute HCl and then water, then dried (MgSO4) and solvent vacuum evaporated to give a colorless liquid. Flash column chromatography of the latter on silica, eluting with hexane-ethyl acetate (7:3) gave, after workup, a liquid which crystallized on standing. Recrystallization from hexane containing a small amount of ethyl acetate gave 2.3 grams (0.01 mole) of methyl 3-[(4-bromo-2-fluorophenyl)amino]-2-methoxy-3-oxopropanaote having a melting point of 51° C.-53° C. Elemental analysis of the product indicated the following:

1. temperaturewhile cooling the reaction mixture in an ice-water bath
2. waitcontinued for an approximate 65-hour period
3. customThe precipitated 1,3-dicyclohexylurea by-product (3.15 grams) was removed by filtration
4. customthe filtrate vacuum evaporated
5. dissolutionthe residue dissolved in methylene chloride
6. extractionThe latter solution was extracted with dilute HCl
7. dry with materialwater, then dried (MgSO4) and solvent vacuum
8. customevaporated
9. customto give a colorless liquid
10. washFlash column chromatography of the latter on silica, eluting with hexane-ethyl acetate (7:3)
11. customgave
12. customafter workup, a liquid which crystallized
13. customRecrystallization from hexane containing a small amount of ethyl acetate
14. customgave 2.3 grams (0.01 mole) of methyl 3-[(4-bromo-2-fluorophenyl)amino]-2-methoxy-3-oxopropanaote having a melting point of 51° C.-53° C