반응 #46971

반응 방정식

2-mercaptobenzothiazolyl (Z)-(2-aminothiazol-4-yl)-2-(trityloxyimino)acetate

7-amino-3-vinyl-3-cephem-4-carboxylic acid

triethylamine

→

N,N′-Dicyclohexylethylenediamine

7β-[2-(2-amino-4-thiazolyl)-2-(Z-hydroxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylic acid

용매

THF

tetrahydrofuran

water

반응 조건

후처리

1. 1
   workup.ADDITIONwas added drop-wise at 20±2° C. over 30-45 minutes
2. 2
   기타was completely removed under vacuum at 28-30° C
3. 3
   workup.ADDITIONTo the concentrated mass, acetone (300 mL) was added
4. 4
   workup.STIRRINGstirred at 30° C.
5. 5
   workup.ADDITION1:1 Hydrochloric acid (200 mL) was added
6. 6
   온도the temperature was raised to 63-64° C
7. 7
   온도At this temperature, it was refluxed for about 35 min
8. 8
   기타to 30° C.
9. 9
   workup.ADDITIONEDTA (0.5 g) was added
10. 10
    workup.STIRRINGstirred for 10 min at 30-35° C.
11. 11
    기타was adjusted to 2.5 using Triethyl amine (100 mL) at 30-35° C
12. 12
    workup.ADDITIONTo the reaction mixture hot solution of N,N′-Dicyclohexylethylenediamine (DDA) 40.0 g in Isopropyl alcohol (100 mL) was added slowly
13. 13
    workup.STIRRINGstirred for 1.0 hour at 30-35° C
14. 14
    여과The precipitated material was filtered
15. 15
    세척washed with acetone
16. 16
    기타dried under vacuum at ˜40° C.

실험 절차

To a chilled suspension of 7-amino-3-vinyl-3-cephem-4-carboxylic acid (50 gm) in a mixture of tetrahydrofuran (250 ml) and water (31.5 ml), triethylamine (45 gm) was added drop-wise at 20±2° C. over 30-45 minutes. 2-mercaptobenzothiazolyl (Z)-(2-aminothiazol-4-yl)-2-(trityloxyimino)acetate (130 gm) was added to the clear solution and the resulting mixture was stirred at 32±2° C. for 4-6 hours. The reaction was monitored by HPLC. After the completion of reaction, THF was completely removed under vacuum at 28-30° C. To the concentrated mass, acetone (300 mL) was added and stirred at 30° C., 1:1 Hydrochloric acid (200 mL) was added and the temperature was raised to 63-64° C. At this temperature, it was refluxed for about 35 min and then cold acetone of 1.8 Liter dumped to the reaction mass to bring down the temperature to 30° C., EDTA (0.5 g) was added and stirred for 10 min at 30-35° C., pH of the solution was adjusted to 2.5 using Triethyl amine (100 mL) at 30-35° C. To the reaction mixture hot solution of N,N′-Dicyclohexylethylenediamine (DDA) 40.0 g in Isopropyl alcohol (100 mL) was added slowly to adjust the pH of the solution 5.5 and stirred for 1.0 hour at 30-35° C. The precipitated material was filtered, washed with acetone and dried under vacuum at ˜40° C. to get N,N′-Dicyclohexylethylenediamine salt of 7β-[2-(2-amino-4-thiazolyl)-2-(Z-hydroxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylic acid. Step-ii

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