Diethyl Ether → (4-Pyridylthiomethyl]-7-[(2,5-dichlorophenyl)-thioacetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 53607

Reaction equation

HRID 53607 reaction equation
IC[C:3]1[CH2:10][S:9][C@H:8]2[N:5]([C:6](=[O:23])[C@H:7]2[NH:11][C:12](=[S:22])[CH2:13][C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[Cl:21])[C:4]=1[C:24]([O-:26])=[O:25].[SH:27][C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1.N1C(C)=CC=C[C:35]=1C.CCOCC>C1COCC1.C(OCC)(=O)C>[N:31]1[CH:32]=[CH:33][C:28]([S:27][CH2:35][O:26][C:24]([C:4]2[N:5]3[CH:8]([S:9][CH2:10][CH:3]=2)[CH:7]([NH:11][C:12](=[S:22])[CH2:13][C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[Cl:21])[C:6]3=[O:23])=[O:25])=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 79372,6-LutidineHCID 86749943(6R)-trans-3-Iodomethyl-7-[(2,5-dichlorophenyl)thioacetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 178418431pyridine-4-thiol

Product 1

HCID 86749942(4-Pyridylthiomethyl]-7-[(2,5-dichlorophenyl)-thioacetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(6R)-trans-3-Iodomethyl-7-[(2,5-dichlorophenyl)thioacetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, diphenylmethyl ester (3.00 g, 4.14 mmol) was dissolved in THF (50 mL) at 0° C. and treated with 4-mercaptopyridine (0.504 g, 4.54 mmol). A solution of 2,6-lutidine (0.576 g, 5.38 mmol) in THF (1 mL) was added next, and the reaction mixture was stirred at 0° C. for 0.5 h and then at 20° C. for 1 h. The mixture was diluted with ethyl acetate (500 mL) and the organic solution was washed with water (2×500 mL) and brine (100 mL). The solution was then dried (MgSO4) and evaporated under reduced pressure to give an oil which was treated with Et2O (50 mL) to give a solid. The solid was collected by filtration and purified by column chromatography on silica gel (CH2Cl2 to 30% EtOAc/CH2Cl2) to give 1.50 g of (6R)-trans-3-[(4-pyridylthiomethyl]-7-[(2,5-dichlorophenyl)thioacetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, diphenylmethyl ester as a tan solid (49% yield), m.p. 122° C. 1H NMR (300 MHz, CDCl3) δ3.37 (d, J=18 Hz, 1H), 3.52 (d, J=18 Hz, 1H), 3.68 (d, J=17 Hz, 1H), 3.76 (d, J=17 Hz, 1H), 3.96 (d, J=13 Hz, 1H), 4.16 (d, J=13 Hz, 1H), 4.93 (d, J=5 Hz, 1H), 5.76 (dd, J=5, 9 Hz, 1H), 6.95-7.42 (m, 16H), 7.49 (d, J=9 Hz, 1H), 8.29 (d, J=6 Hz, 2H). Anal. Calcd. for C34H27N3O4S3Cl2 : C, 57.62; H, 3.84; N, 5.93. Found: C, 57.27; H, 3.68; N, 5.79.

Workup

  1. waitat 20° C. for 1 h
  2. washthe organic solution was washed with water (2×500 mL) and brine (100 mL)
  3. dry with materialThe solution was then dried (MgSO4)
  4. customevaporated under reduced pressure
  5. customto give an oil which
  6. customto give a solid
  7. filtrationThe solid was collected by filtration
  8. custompurified by column chromatography on silica gel (CH2Cl2 to 30% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-2ae62cefb7c845b19cd78a5ea1e467df
Source dataset
uspto-grants-1997_04
Patent number
US05620969

Linked notes

Loading…