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Phosphorus oxychloride → 7-[2-methoxyimino-2-{2-(2,2,2-trifluoroacetamido)thiazol-4-yl}acetamido]-3-[1-(2-carboxy-2-methoxyiminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

HRID 2412580
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HRID 2412580 반응식
[CH3:1][O:2][N:3]=[C:4]([C:8]1[N:9]=[C:10]([NH:13][C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[S:11][CH:12]=1)[C:5]([OH:7])=O.C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[NH2:31][CH:32]1[C:57](=[O:58])[N:34]2[C:35]([C:54]([OH:56])=[O:55])=[C:36]([CH2:39][S:40][C:41]3[N:45]([CH2:46][C:47]([C:51]([OH:53])=[O:52])=[N:48][O:49][CH3:50])[N:44]=[N:43][N:42]=3)[CH2:37][S:38][C@H:33]12.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O1CCCC1.O.CC(C)=O.CN(C=O)C>[CH3:1][O:2][N:3]=[C:4]([C:8]1[N:9]=[C:10]([NH:13][C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[S:11][CH:12]=1)[C:5]([NH:31][CH:32]1[C:57](=[O:58])[N:34]2[C:35]([C:54]([OH:56])=[O:55])=[C:36]([CH2:39][S:40][C:41]3[N:45]([CH2:46][C:47]([C:51]([OH:53])=[O:52])=[N:48][O:49][CH3:50])[N:44]=[N:43][N:42]=3)[CH2:37][S:38][C@H:33]12)=[O:7]
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참가 물질

11

반응물 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 516892Sodium BicarbonateHCID 540662192-Methoxyimino-2-(2-trifluoroacetylaminothiazol-4-yl)acetic acidHCID 1317132437-amino 3-[1-(2-carboxy-2-methoxyiminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

생성물 1

HCID 131713244
7-[2-methoxyimino-2-{2-(2,2,2-trifluoroacetamido)thiazol-4-yl}acetamido]-3-[1-(2-carboxy-2-methoxyiminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

시약·촉매·용매 5

HCID 180Acetone용매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매2회

실험 절차

2-Methoxyimino-2-[2-(2,2,2-trifluoroacetamido)thiazol-4-yl]acetic acid (syn isomer) (0.97 g) was added at 0° C. to vilsmeier reagent which had been prepared from N,N,-dimethylformamide (0.31 g) and phosphoryl chloride (0.65 g) in ethyl acetate (1.2 ml) and tetrahydrofuran (7.4 ml), and the mixture was stirred at the same temperature for 30 minutes to afford the activated solution. The activated solution was added dropwise at -5 to 0 C. to a solution of 7-amino-3-[1-(2-carboxy-2-methoxyiminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (1.40 g) in water (10 ml) and acetone (8 ml), adjusted to pH 8.0 with sodium bicarbonate and the mixture was stirred at the same temperature for 45 minutes. To the resultant mixture was added ethyl acetate (10 ml), and the aqueous phase was separated from the mixture. To the aqueous solution was added ethyl acetate (70 ml) and the mixture was adjusted to pH 2.0 with 10% hydrochloric acid with stirring, and the ethyl acetate layer was separated, washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated. The residue was pulverized with diisopropyl ether to give 7-[2-methoxyimino-2-{2-(2,2,2-trifluoroacetamido)thiazol-4-yl}acetamido]-3-[1-(2-carboxy-2-methoxyiminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer: in the 7-position) (1.77 g), mp 164° to 170° C. (dec.).

후처리

  1. customto afford the activated solution
  2. additionThe activated solution was added dropwise at -5 to 0 C
  3. stirringthe mixture was stirred at the same temperature for 45 minutes
  4. customthe aqueous phase was separated from the mixture
  5. additionTo the aqueous solution was added ethyl acetate (70 ml)
  6. stirringwith stirring
  7. customthe ethyl acetate layer was separated
  8. washwashed with a saturated aqueous solution of sodium chloride
  9. dry with materialdried over magnesium sulfate
  10. customevaporated

출처 및 근거

ORD 기록
ord-74c1a299db1c4de4a245b43a2e2e77cc
출처 데이터셋
uspto-grants-1985_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US04493834

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