تفاعل #56567

معادلة التفاعل

2-methyl-7-amino-3-cephem-4-carboxylic acid

sodium bicarbonate

2-methoxyimino-2-(2-aminothiazol-4-yl)acetic acid

trimethylsilylacetamide

phosphorus oxychloride

phosphorus oxychloride

sodium bicarbonate

2-methoxyimino-2-(2-imino-2,3-dihydrothiazol-4-yl)acetic acid

→

2-methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

المذيبات

acetone

water

ethyl acetate

ethyl acetate

dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooling
2. 2
   workup.STIRRINGthe mixture was stirred for 30 minutes at 4° to 6° C
3. 3
   workup.STIRRINGwith stirring under ice-
4. 4
   درجة الحرارةcooling
5. 5
   workup.STIRRINGthe mixture was stirred for 30 minutes at 4° to 6° C.
6. 6
   workup.STIRRINGwith stirring under ice-
7. 7
   درجة الحرارةcooling
8. 8
   workup.ADDITIONwas added dropwise
9. 9
   workup.STIRRINGThe mixture was stirred for 40 minutes at the same temperature
10. 10
    درجة الحرارةthe resulting clear solution was cooled to -10° C
11. 11
    درجة الحرارةthe mixture was cooled to -5° C
12. 12
    workup.ADDITIONTo the mixture was added dropwise the above prepared clear solution at -5° to 0° C.
13. 13
    workup.STIRRINGthe mixture was stirred for 2 hours
14. 14
    أخرىthe aqueous layer was separated
15. 15
    أخرىprecipitated crystals
16. 16
    ترشيحwere collected by filtration
17. 17
    غسيلwashed with water and acetone in turn
18. 18
    أخرىdried under reduced pressure

الإجراء التجريبي

A suspension of 2-methoxyimino-2-(2-aminothiazol-4-yl)acetic acid (syn isomer), which can be represented as 2-methoxyimino-2-(2-imino-2,3-dihydrothiazol-4-yl)acetic acid (syn isomer), (26 g.) in ethyl acetate (250 ml.) was cooled to 5° C., and phosphorus oxychloride (25 g.) was added dropwise thereto with stirring under ice-cooling, and then the mixture was stirred for 30 minutes at 4° to 6° C. To the mixture was added dropwise a solution of trimethylsilylacetamide (22 g.) in ethyl acetate (20 ml.) with stirring under ice-cooling, and the mixture was stirred for 30 minutes at 4° to 6° C., and then phosphorus oxychloride (25 g.) was further added thereto with stirring under ice-cooling. The mixture was stirred for 15 minutes at the same temperature and dimethylformamide (10.6 g.) was added dropwise thereto at the same temperature. The mixture was stirred for 40 minutes at the same temperature, and the resulting clear solution was cooled to -10° C. On the other hand, to a solution of 2-methyl-7-amino-3-cephem-4-carboxylic acid (23.9 g.) in a solution of sodium bicarbonate (25 g.) and water (400 ml.) was added acetone (300 ml.), and the mixture was cooled to -5° C. To the mixture was added dropwise the above prepared clear solution at -5° to 0° C., and then the mixture was stirred for 2 hours, all the while the mixture was kept to pH 6 with 15% aqueous sodium bicarbonate solution. Insoluble materials were filterred off, and the aqueous layer was separated. The aqueous layer was adjusted to pH 3 with 20% hydrochloric acid, and precipitated crystals were collected by filtration, washed with water and acetone in turn and then dried under reduced pressure to give 2-methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), which can be represented as 2-methyl-7 -[2-methoxyimino-2-(2-imino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), (39.4 g.). This object compound was identified with the object compound prepared in Example 6 by IR and NMR determination.

المصدر