Sulfuric Acid → Cefdinir

HRID 2213706

반응식

HRID 2213706 반응식
[NH2:1][CH:2]1[C:14](=[O:15])[N:4]2[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH:9]=[CH2:10])[CH2:7][S:8][C@H:3]12.O1CCCC1.[NH2:21][C:22]1[S:23][CH:24]=[C:25](/[C:27](=[N:41]/[O:42]C(=O)C)/[C:28](OC2C3N=C(S)SC=3C=CC=2)=[O:29])[N:26]=1.S(=O)(=O)(O)O>O.C(Cl)Cl.C(N(CC)CC)C>[NH2:21][C:22]1[S:23][CH:24]=[C:25](/[C:27](=[N:41]/[OH:42])/[C:28]([NH:1][C@@H:2]2[C:14](=[O:15])[N:4]3[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH:9]=[CH2:10])[CH2:7][S:8][C@H:3]23)=[O:29])[N:26]=1

참가 물질

8

반응물 4

HCID 1118Sulfuric AcidHCID 8028TetrahydrofuranHCID 128180067-Amino-3vinyl-3-cephem-4-carboxylic acid2회HCID 178476694HCID 178476694, 화합물

생성물 1

HCID 6915944Cefdinir수율 62.9%

시약·촉매·용매 3

HCID 962Water용매2회HCID 6344Dichloromethane용매HCID 8471Triethylamine용매

실험 절차

40 g of 7-amino-3-vinyl-3-cephem-4-carboxylic acid (AVNA, 0.177 mol) was added to 400 ml of tetrahydrofuran under nitrogen atmosphere followed by 78 g of O-acetyl thioester (0.206 mol, prepared in Example 1) and 200 ml of water with stirring. Cooled the reaction mass to 15–20° C. To this reaction mixture, 20 g of triethylamine was added slowly at pH ˜8.5. Stirring was continued and progress of the reaction was monitored by qualitative HPLC till AVNA was less than 1%. At this stage 400 ml of methylene dichloride was added and stirred for further 15 min at 20–25° C. 200 ml of water was added and stirred the reaction mass for 15 min at 20–25° C. Separated the layers and to the aqueous layer, 20% w/v aqueous potassium carbonate solution was added and maintained pH at 8.1–8.2 at 20–25° C. Thereafter, 26.4 g of ammonium chloride was added in one lot at 20–25° C. and continued maintaining the pH between 8.0 to 8.2 by addition of 20% w/v aqueous potassium carbonate solution. The progress of reaction was monitored by qualitative HPLC till O-acetyl cefdinir is less than 0.5%. Adjusted the pH of reaction mass to 2.4–2.5 with conc. sulfuric acid maintaining temperature between 35° to 40° C. The precipitated product was filtered and dried at 40–45° C. under reduced pressure till moisture content was ≦2% wiw. 44 g of product was obtained in 99.3% purity (by HPLC).

후처리

  1. temperatureCooled the reaction mass to 15–20° C
  2. stirringStirring
  3. stirringstirred for further 15 min at 20–25° C
  4. stirringstirred the reaction mass for 15 min at 20–25° C
  5. customSeparated the layers
  6. additionwas added
  7. temperaturemaintained pH at 8.1–8.2 at 20–25° C
  8. additionThereafter, 26.4 g of ammonium chloride was added in one lot at 20–25° C.
  9. temperaturecontinued maintaining the pH between 8.0 to 8.2
  10. additionby addition of 20%
  11. customThe progress of reaction
  12. filtrationThe precipitated product was filtered
  13. customdried at 40–45° C. under reduced pressure till moisture content

출처 및 근거

ORD 기록
ord-ec1b8ddfb5a343738a259eb80bb9de58
출처 데이터셋
uspto-grants-2006_09
특허 번호
US07105659B2

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