Triethylamine → (6R,7R)-3-(carbamoyloxymethyl)-7-[[2-(2-furanyl)-2-methoxyimino-1-oxoethyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 1283149Notes

Reaction equation

HRID 1283149 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.[O:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:12](=[N:16][O:17][CH3:18])[C:13]([OH:15])=O.[NH2:19][C@@H:20]1[C:39](=[O:40])[N:22]2[C:23]([C:36]([OH:38])=[O:37])=[C:24]([CH2:27][O:28][C:29](=[O:35])[NH:30]C(=O)CCl)[CH2:25][S:26][C@H:21]12.C(N(CC)CC)C>ClCCl.CO.CN(C)C(=O)C>[C:29]([O:28][CH2:27][C:24]1[CH2:25][S:26][C@@H:21]2[C@H:20]([NH:19][C:13](=[O:15])[C:12]([C:8]3[O:7][CH:11]=[CH:10][CH:9]=3)=[N:16][O:17][CH3:18])[C:39](=[O:40])[N:22]2[C:23]=1[C:36]([OH:38])=[O:37])(=[O:35])[NH2:30]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 24819Phosphorus pentachlorideHCID 2724574alpha-(Methoxyimino)furan-2-acetic acidHCID 12884123(6R,7R)-7-amino-3-chloroacetylcarbamoyloxymethylceph-3-em-4-carboxylic acid

Product 1

HCID 41375(6R,7R)-3-(carbamoyloxymethyl)-7-[[2-(2-furanyl)-2-methoxyimino-1-oxoethyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 90.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

N,N-Dimethylacetamide (1.5 ml) was added to a solution of phosphorus pentachloride (750mg, 3.6mmole) in anhydrous dichloromethane (15ml) cooled to -10°. After 10 minutes, 2-(fur-2-yl)-2-methoxyiminoacetic acid (syn isomer) (612mg, 3.6mmole) was added to the resulting suspension, which soon became a clear solution and was stirred at -10° for 15 minutes. Ice (3g) was added and after 10 minutes the layers were allowed to separate in a dropping funnel. The organic phase was slowly (over 5 minutes) run into a cooled (-10°) solution of (6R,7R)-7-amino-3-chloroacetylcarbamoyloxymethylceph-3-em-4-carboxylic acid (1.05g, 3mmole) in dichloromethane (15ml) containing triethylamine (0.9ml, 6.5mmole). Methanol (1ml) was added after 40 minutes, and 5 minutes later the reaction mixture was extracted twice with 3% w/v aqueous sodium bicarbonate solution (150ml). The aqueous extract was washed with ethyl acetate (25ml) and left at 20° for 4 hours. The solution was washed twice with ethyl acetate, acidified with 2N-hydrochloric acid, and extracted 3 times with ethyl acetate. The combined organic layers were dried over magnesium sulphate, decolourised with activated charcoal, and evaporated in vacuo to give a pale-yellow solid (1.15g, 87%). This was washed with diethyl ether and filtered off to give the title compound (0.91g,71%); λmaxpH6 274nm (ε17,300). The IR and NMR spectra of the product agreed with those of an authentic sample.

Workup

  1. temperaturecooled to -10°
  2. customto separate in a dropping funnel
  3. custom(over 5 minutes)
  4. extraction5 minutes later the reaction mixture was extracted twice with 3% w/v aqueous sodium bicarbonate solution (150ml)
  5. extractionThe aqueous extract
  6. washwas washed with ethyl acetate (25ml)
  7. waitleft at 20° for 4 hours
  8. washThe solution was washed twice with ethyl acetate
  9. extractionextracted 3 times with ethyl acetate
  10. dry with materialThe combined organic layers were dried over magnesium sulphate
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-da9875bffbb84d8f9e81c27312563155
Source dataset
uspto-grants-1976_08
Patent number
US03974153

Reaction notes

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