Diisopropyl Ether → HCID 131714462, compound

HRID 638087Notes

Reaction equation

HRID 638087 reaction equation
[Br:1][CH2:2][C:3](=O)[CH2:4][C:5]([NH:7][CH:8]1[C:33](=[O:34])[N:10]2[C:11]([C:17]([O:19][CH:20]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])=[C:12]([CH:15]=[CH2:16])[CH2:13][S:14][C@H:9]12)=[O:6].[N:36]([O:38]CCC(C)C)=O.C(CC(=O)C)(=O)C.[NH2:51][C:52]([NH2:54])=[S:53].C(OC(C)C)(C)C>C(Cl)Cl.C(O)(=O)C.C(OCC)(=O)C>[BrH:1].[NH2:54][C:52]1[S:53][CH:2]=[C:3]([C:4](=[N:36][OH:38])[C:5]([NH:7][CH:8]2[C:33](=[O:34])[N:10]3[C:11]([C:17]([O:19][CH:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)=[O:18])=[C:12]([CH:15]=[CH2:16])[CH2:13][S:14][C@H:9]23)=[O:6])[N:51]=1

Participants

9

Reactant 5

HCID 7914Diisopropyl EtherHCID 8053Isoamyl NitriteHCID 31261AcetylacetoneHCID 2723790ThioureaHCID 13336158HCID 13336158, compound

Product 1

HCID 131714462HCID 131714462, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-5 °C

Procedure

To a solution of benzhydryl 7-(4-bromoacetoacetamido)-3-vinyl-3-cephem-4-carboxylate (10 g) in a mixture of methylene chloride (70 ml) and acetic acid (25 ml) was dropwise added isoamyl nitrite (3.5 ml) at -3° to -5° C. The mixture was stirred for 40 minutes at -5° C., followed by addition of acetylacetone (4 g) and stirring for 30 minutes at 5° C. To the reaction mixture was added thiourea (3 g) and after stirring for 3 hours, thereto were added dropwise ethyl acetate (70 ml) and diisopropyl ether (100 ml). The resultant precipitate was collected by filtration and dried in vacuo to give benzhydryl 7-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylate hydrobromide (syn isomer) (11.7 g). 3 g of this product was added portionwise to a mixture of 2,2,2-trifluoroacetic acid (5 ml) and anisole (5 ml) at 5° to 7° C. After stirring for 1 hour at 5° C., the reaction mixture was added dropwise to diisopropyl ether (150 ml). The resultant precipitate was collected by filtration and dissolved in a mixture of tetrahydrofuran (10 ml) and ethyl acetate (10 ml). The organic layer was extracted with an aqueous sodium bicarbonate. The aqueous extract was washed with ethyl acetate under keeping the pH value at 5 and then adjusted to pH 2.2 with 10% hydrochloric acid. This solution was stirred for 1 hour at 0° C., and the obtained crystals were collected by filtration and dried in vacuo to give 7-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylic acid (syn isomer) (0.79 g).

Workup

  1. customat -3° to -5° C
  2. stirringstirring for 30 minutes at 5° C
  3. stirringafter stirring for 3 hours
  4. filtrationThe resultant precipitate was collected by filtration
  5. customdried in vacuo

Sources & evidence

ORD record
ord-51ea06019e1e4b619723b9c6e08c9604
Source dataset
uspto-grants-1985_12
Patent number
US04559334

Reaction notes

Loading…