N,N-Dimethylaniline → (2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(3S,5S)-1,5-bis[(4-nitrophenyl)methoxycarbonyl]pyrrolidin-3-yl]oxyiminoacetic acid

HRID 1194943Notes

Reaction equation

HRID 1194943 reaction equation
O=[C:2]([CH3:44])/[C:3](=[N:11]/[O:12][C@@H:13]1[CH2:17][N:16]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=2)=[O:19])[C@H:15]([C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=2)=[O:32])[CH2:14]1)/[C:4]([O:6]C(C)(C)C)=[O:5].S(Cl)(Cl)(=O)=O.[NH2:50][C:51]([NH2:53])=[S:52].CN(C)C1C=CC=CC=1>C(O)(=O)C.C(O)C>[NH2:53][C:51]1[S:52][CH:44]=[C:2](/[C:3](=[N:11]/[O:12][C@@H:13]2[CH2:17][N:16]([C:18]([O:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]([N+:28]([O-:30])=[O:29])=[CH:26][CH:27]=3)=[O:19])[C@H:15]([C:31]([O:33][CH2:34][C:35]3[CH:36]=[CH:37][C:38]([N+:41]([O-:43])=[O:42])=[CH:39][CH:40]=3)=[O:32])[CH2:14]2)/[C:4]([OH:6])=[O:5])[N:50]=1

Participants

7

Reactant 4

HCID 949N,N-DimethylanilineHCID 24648Sulfuryl chlorideHCID 2723790ThioureaHCID 140352850bis[(4-nitrophenyl)methyl] (2S,4S)-4-[(Z)-[1-[(2-methylpropan-2-yl)oxy]-1,3-dioxobutan-2-ylidene]amino]oxypyrrolidine-1,2-dicarboxylate

Product 1

HCID 88627828(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(3S,5S)-1,5-bis[(4-nitrophenyl)methoxycarbonyl]pyrrolidin-3-yl]oxyiminoacetic acidYield 92.8%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

tert-Butyl 3-oxo-(Z)-2-[(2S,4S)-1-(4-nitrobenzyloxycarbonyl)-2-(4-nitrobenzyloxycarbonyl)pyrrolidine-4-yloxyimino]butyrate (2.19 g, 3.56 mmol) in acetic acid (7 ml) was treated with sulphuryl chloride (2.89 ml, 4.81 g, 35.6 mmol) and the mixture was heated at 50° C. for 2.75 h. The mixture was evaporated under reduced pressure, and toluene added to the residue an the solvent evaporated. The was repeated a further three times. The residue was partially dissolved in ethanol (15 ml) and thiourea (271 mg, 3.56 mmol) was added, followed by N,N-dimethylaniline (0.9 ml, 860 mg, 7.1 mmol). Ethanol (15 ml) was added and the mixture was warmed to effect dissolution, the mixture was stirred at room temperture for 1.5 h, then warmed again to dissolve the material, and stirred a further 0.5 h. The ethanol was then removed by evaporation under reduced pressure and a mixture of water/ethyl acetate/n-butanol added. The pH was adjusted to 2 and the layers separated. The aqueous layer was again extracted with n-butanol (x2). The butanol extracts were combined and evaporated under reduced pressure. Ethanol was added to the residue and removed under reduced pressure, followed by toluene (x3) to leave a solid which was dried over P2O5 in vacuo to give the crude title compound (2.03 g); νmax (KBr) 3383, 1745, 1710, 1630, 1607, 1521, 1432, 1404 and 1347 cm-1.

Workup

  1. customThe mixture was evaporated under reduced pressure, and toluene
  2. additionadded to the residue an the solvent
  3. customevaporated
  4. dissolutionThe residue was partially dissolved in ethanol (15 ml)
  5. temperaturethe mixture was warmed
  6. dissolutiondissolution
  7. temperaturewarmed again
  8. dissolutionto dissolve the material
  9. stirringstirred a further 0.5 h
  10. customThe ethanol was then removed by evaporation under reduced pressure
  11. additiona mixture of water/ethyl acetate/n-butanol
  12. additionadded
  13. customthe layers separated
  14. extractionThe aqueous layer was again extracted with n-butanol (x2)
  15. customevaporated under reduced pressure
  16. additionEthanol was added to the residue
  17. customremoved under reduced pressure
  18. customto leave a solid which
  19. dry with materialwas dried over P2O5 in vacuo

Sources & evidence

ORD record
ord-557a8389f42d47b6992ed28396419f81
Source dataset
uspto-grants-1989_03
Patent number
US04816452

Reaction notes

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