Acetic Acid → (E)-(6R,7R)-3-[1-(4-Amino-benzyl)-2-oxo-pyrrolidin-3-ylidenemethyl]-8-oxo-7-(2-phenylsulfanyl-acetylamino)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 1597702Notes

Reaction equation

HRID 1597702 reaction equation
N1C=CN=C1.C(OC([NH:12][C:13]1[CH:49]=[CH:48][C:16]([CH2:17][N:18]2[CH2:22][CH2:21]/[C:20](=[CH:23]\[C:24]3[CH2:31][S:30][C@H:29]4[N:26]([C:27](=[O:43])[C@H:28]4[NH:32][C:33](=[O:42])[CH2:34][S:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[C:25]=3[C:44]([OH:46])=[O:45])/[C:19]2=[O:47])=[CH:15][CH:14]=1)=O)C=C.C[Si](/N=C(/O[Si](C)(C)C)\C(F)(F)F)(C)C.C(O)(=O)C.C([SnH](CCCC)CCCC)CCC.Cl>ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)C>[NH2:12][C:13]1[CH:49]=[CH:48][C:16]([CH2:17][N:18]2[CH2:22][CH2:21]/[C:20](=[CH:23]\[C:24]3[CH2:31][S:30][C@H:29]4[N:26]([C:27](=[O:43])[C@H:28]4[NH:32][C:33](=[O:42])[CH2:34][S:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[C:25]=3[C:44]([OH:46])=[O:45])/[C:19]2=[O:47])=[CH:15][CH:14]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5948TributylstannaneHCID 5366669trimethylsilyl (1E)-2,2,2-trifluoro-N-trimethylsilylethanimidateHCID 69468988(E)-(6R,7R)-3-[1-(4-allyloxycarbonylamino-benzyl)-2-oxo-pyrrolidin-3-ylidenemethyl]-8-oxo-7-(2-phenylsulfanyl-acetylamino)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid imidazole salt

Product 1

HCID 69466517(E)-(6R,7R)-3-[1-(4-Amino-benzyl)-2-oxo-pyrrolidin-3-ylidenemethyl]-8-oxo-7-(2-phenylsulfanyl-acetylamino)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

(E)-(6R,7R)-3- [1-(4-allyloxycarbonylamino-benzyl)-2-oxo-pyrrolidin-3-ylidenemethyl]-8-oxo-7-(2-phenylsulfanyl-acetylamino)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid imidazole salt (1:1) (400.0 mg, 0.57 mmol) was suspended in 20 ml dichloromethane and treated with N,O-bis(trimethylsilyl)-trifluoroacetamide (240.7 ml, 9.11 mmol). After 15 min, bis(triphenylphosphine)palladium(II) chloride (10.0 mg, 0.014 mmol), acetic acid (0.65 ml, 11.4 mmol) and tributyltin hydride (1.53 ml, 5.70 mmol) were added. After 45 min the suspension was poured under stirring on 250 ml diethyl ether, containing 3 ml of a hydrochloric acid-saturated diethyl ether solution and was stirred for 1 h. The solid material was collected by filtration, suspended in 4 ml water: acetonitrile (1:1) and the pH was adjusted to 2 with 1M hydrochloric acid. To the suspension an equal amount of MCI gel (75-150μ, Mitsubishi Kasei Corporation) was added, the organic solvent was evaporated and the residue was chromatographed on MCI gel (75-150μ, Mitsubishi Kasei Corporation) with a gradient of water:acetonitrile (9:1, 4:1, 2:1, 1:1, 1:3). The organic solvent was evaporated and the aqueous phase was freeze-dried.

Workup

  1. additionAfter 45 min the suspension was poured
  2. filtrationThe solid material was collected by filtration
  3. additionTo the suspension an equal amount of MCI gel (75-150μ, Mitsubishi Kasei Corporation) was added
  4. customthe organic solvent was evaporated
  5. customthe residue was chromatographed on MCI gel (75-150μ, Mitsubishi Kasei Corporation) with a gradient of water:acetonitrile (9:1, 4:1, 2:1, 1:1, 1:3)
  6. customThe organic solvent was evaporated
  7. customthe aqueous phase was freeze-dried

Sources & evidence

ORD record
ord-f19a5a1399bc474a8e94e2f1be75a3bb
Source dataset
uspto-grants-2001_09
Patent number
US06294668B1

Reaction notes

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