HRID1902960

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID24813

Phosphoric trichloride

Cl3OP

HCID77311

未命名化合物

HCID357676

Acetamide, 2-(trimethylsilyl)-

C5H13NOSi

结构：CC(C)(C)OC(=O)NCc1nnc(SCC2=C(C(=O)O)N3C(=O)C(N)[C@H]3SC2)s1

HCID14207412

未命名化合物

结构：CC(C)(C)OC(=O)NCCCON=C(C(=O)O)c1csc(NC=O)n1

HCID54026643

未命名化合物

PRODUCTS

生成物

HCID77311

未命名化合物

结构：CC(C)(C)OC(=O)NCCCON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(CSc3nnc(CNC(=O)OC(C)(C)C)s3)CS[C@H]12)c1csc(NC=O)n1

HCID131712916

未命名化合物

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID962

Water

H2O

溶剂HCID6228

N,N-Dimethylformamide

C3H7NO

溶剂HCID8857

Ethyl acetate

C4H8O2

3 次

PROCEDURE

实验过程

Vilsmeier reagent was prepared from N,N-dimethyl-formamide (0.65 g.) and phosphoryl chloride (1.4 g.) in a usual manner. 2-(2-Formamidothiazol-4-yl)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetic acid (syn isomer, 3.0 g.) was added to a stirred suspension of the Vilsmeier reagent in ethyl acetate (30 ml.) under ice-cooling and stirred at the same temperature for 30 minutes [Solution A]. Trimethylsilylacetamide (8.1 g.) was added to a stirred suspension of 7-amino-3-(5-tert-butoxycarbonylaminomethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (3.7 g.) in ethyl acetate (40 ml.) and stirred at room temperature for 30 minutes. The solution A was added to the solution all at once at -30° C., and stirred at -10° to -40° C. for an hour. Water and ethyl acetate (100 ml.) were added to the resultant mixture at -10° C., and the ethyl acetate layer was separated. Water (100 ml.) was added to the ethyl acetate layer and adjusted to pH 7.0 with saturated aqueous sodium bicarbonate solution. The aqueous layer was separated. Ethyl acetate was added to the solution and adjusted to pH 3.8 with 10% hydrochloric acid under ice-cooling. The ethyl acetate layer was separated and washed with saturated sodium chloride solution. The solution was dried over magnesium sulfate and concentrated in vacuo. The residue was pulverized with diisopropyl ether to give 7-[2-(2-formamidothiazol-4-yl)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetamido]-3-(5-tert-butoxycarbonylaminomethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 1.6 g.).

WORKUP

后处理

temperaturecooling
stirringstirred at -10° to -40° C. for an hour
customthe ethyl acetate layer was separated
additionWater (100 ml.) was added to the ethyl acetate layer and adjusted to pH 7.0 with saturated aqueous sodium bicarbonate solution
customThe aqueous layer was separated
additionEthyl acetate was added to the solution
temperaturecooling
customThe ethyl acetate layer was separated
washwashed with saturated sodium chloride solution
dry with materialThe solution was dried over magnesium sulfate
concentrationconcentrated in vacuo

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-13dcf26951144d989b28d1378dd81939
来源数据集: uspto-grants-1982_12
DOI: 10.6084/m9.figshare.5104873.v1
专利: US04366153
来源说明: uspto-grants-1982_12

反应 SMILES

P(Cl)(Cl)([Cl:3])=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[CH3:31][N+:32]([CH3:35])=[CH:33][Cl:34].[Cl-].C[Si](CC(N)=O)(C)C.[NH2:45][CH:46]1[C:72](=[O:73])[N:48]2[C:49]([C:69]([OH:71])=[O:70])=[C:50]([CH2:53][S:54][C:55]3[S:56][C:57]([CH2:60][NH:61][C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])=[N:58][N:59]=3)[CH2:51][S:52][C@H:47]12>C(OCC)(=O)C.O.CN(C)C=O>[CH3:31][N+:32]([CH3:35])=[CH:33][Cl:34].[Cl-:3].[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:15]([NH:45][CH:46]2[C:72](=[O:73])[N:48]3[C:49]([C:69]([OH:71])=[O:70])=[C:50]([CH2:53][S:54][C:55]4[S:56][C:57]([CH2:60][NH:61][C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])=[N:58][N:59]=4)[CH2:51][S:52][C@H:47]23)=[O:17])[N:13]=1)=[O:7]