Water → (E)-(6R,7R)-7-[(R)-2-bromo-propionylamino]-3-[3-(carbamoylmethyl-dimethyl-ammonio)-propenyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1370689Notes

Reaction equation

HRID 1370689 reaction equation
I.[NH2:2][C@@H:3]1[C:10](=[O:11])[N:9]2[C@@H:4]1[S:5][CH2:6][C:7](/[CH:15]=[CH:16]/[CH2:17][N+:18]([CH2:21][C:22](=[O:24])[NH2:23])([CH3:20])[CH3:19])=[C:8]2[C:12]([O-:14])=[O:13].[Br:25][C@H:26]([CH3:30])[C:27](Cl)=[O:28].C(OCC)C.O>ClCCl.C(#N)C>[Br:25][C@H:26]([CH3:30])[C:27]([NH:2][C@@H:3]1[C:10](=[O:11])[N:9]2[C@@H:4]1[S:5][CH2:6][C:7](/[CH:15]=[CH:16]/[CH2:17][N+:18]([CH2:21][C:22](=[O:24])[NH2:23])([CH3:20])[CH3:19])=[C:8]2[C:12]([O-:14])=[O:13])=[O:28]

Participants

6

Reactant 4

HCID 962WaterHCID 3283Diethyl EtherHCID 6997261(2R)-2-bromopropionyl chlorideHCID 86759025(E)-(6R,7R)-7-amino-3-[3-(carbamoylmethyl-dimethyl-ammonio)-propenyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate monohydroiodide

Product 1

HCID 86759023(E)-(6R,7R)-7-[(R)-2-bromo-propionylamino]-3-[3-(carbamoylmethyl-dimethyl-ammonio)-propenyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylateYield 91.5%

Reagents, catalysts & solvents 1

HCID 21877088Acetonitrile methylene chlorideSolvent

Procedure

To a suspension of 1.4 g (E)-(6R,7R)-7-amino-3-[3-(carbamoylmethyl-dimethyl-ammonio)-propenyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate monohydroiodide in 24 ml of dichloromethane/acetonitrile (1:1) was added 4 ml of N,O-Bis(trimethylsilanyl)trifluoroacetamide and the mixture was stirred at 20° for 0.5 h. After cooling of the reaction mixture to 0°, 2.05 g of (R)-2-bromo-propionyl chloride was added and stirring was continued for 5 min. The solution was dropped onto 0.5 l of diethyl ether containing 0.2 ml of water. The mixture was stirred for 0.5 h and subsequently, the precipitate was isolated by filtration, washed with 50 ml of diethyl ether, and dried. The brown solid was suspended in 5 ml of water. After adjusting the pH to 2.5 by the addition of 2N NaOH, 0.3 l of 2-propanol were added and the mixture was stirred at 20° for 0.5 h. The precipitate was filtered off, washed with 50 ml of diethyl ether and dried, to give 1.3 g of (E)-(6R,7R)-7-[(R)-2-bromo-propionylamino]-3-[3-(carbamoylmethyl-dimethyl-ammonio)-propenyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate as a light-brown powder.

Workup

  1. temperatureAfter cooling of the reaction mixture to 0°
  2. stirringstirring
  3. waitwas continued for 5 min
  4. stirringThe mixture was stirred for 0.5 h
  5. customsubsequently, the precipitate was isolated by filtration
  6. washwashed with 50 ml of diethyl ether
  7. customdried
  8. additionby the addition of 2N NaOH, 0.3 l of 2-propanol
  9. additionwere added
  10. stirringthe mixture was stirred at 20° for 0.5 h
  11. filtrationThe precipitate was filtered off
  12. washwashed with 50 ml of diethyl ether
  13. customdried

Sources & evidence

ORD record
ord-7d04d96c74524ca4b5515a87af0ffb44
Source dataset
uspto-grants-2003_06
Patent number
US06583133B1

Reaction notes

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