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Pyridine → Benzhydryl 7-amino-3-cephem-4-carboxylate

HRID 1905806
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HRID 1905806 반응식
[C:1]1([CH:7]([O:14][C:15]([CH:17]2[N:22]3[C:23](=[O:35])[C@@H:24]([NH:25]C(=O)CC4C=CC=CC=4)[C@H:21]3[S:20][CH2:19][CH:18]2OS(C)(=O)=O)=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl.C(N(CC)CC)C>ClCCl.CO>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:35])[CH:24]([NH2:25])[C@H:21]3[S:20][CH2:19][CH:18]=2)=[O:16])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
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참가 물질

7

반응물 4

HCID 1049PyridineHCID 8471TriethylamineHCID 24819Phosphorus pentachlorideHCID 137854843-Methanesulfonyloxy-7beta-phenylacetylaminocepham-4-carboxylic acid diphenylmethyl ester

생성물 1

HCID 12098365Benzhydryl 7-amino-3-cephem-4-carboxylate수율 55.7%

시약·촉매·용매 2

HCID 887
Methanol
용매
HCID 6344Dichloromethane용매2회

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온도
-30 °C

실험 절차

To a solution of 3-methanesulfonyloxy-7beta-phenylacetylaminocepham-4-carboxylic acid diphenylmethyl ester (3c) in dichloromethane (7 parts) cooling at -25° to -20° C. under nitrogen are added pyridine (2 equivalents) and phosphorus pentachloride (1.7 equivalents). After stirring at -15° to -10° C. for 4 hours, the mixture is diluted with methanol (12 parts) cooled at -40° to -30° C. After stirring for 30 minutes at -30° C. and for 2.5 hours at 0° to 5° C., the mixture is cooled to -30° C., mixed dropwise with triethylamine (8.1 equivalents) and let stand overnight at 0° to 5° C. The mixture is diluted with dichloromethane and ice-water and stirred for 20 minutes at 0° to 5° C. The formed organic layer is taken, washed with hydrochloric acid, water, aqueous sodium hydrogen carbonate, and water, dried, and concentrated. The residue is crystallized from ethyl acetate to give 7beta-amino-3-cephem-4-carboxylic acid diphenylmethyl ester (5). Yield: 55.7%.

후처리

  1. temperaturecooled at -40° to -30° C
  2. stirringAfter stirring for 30 minutes at -30° C. and for 2.5 hours at 0° to 5° C.
  3. waitlet stand overnight at 0° to 5° C
  4. stirringstirred for 20 minutes at 0° to 5° C
  5. washwashed with hydrochloric acid, water, aqueous sodium hydrogen carbonate, and water
  6. customdried
  7. concentrationconcentrated
  8. customThe residue is crystallized from ethyl acetate

출처 및 근거

ORD 기록
ord-862ab793ead84144b84afbda5d94f8d3
출처 데이터셋
uspto-grants-1987_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US04647658

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