Trifluoroacetic acid → 1-(2-Hydroxy-3-amino-1-propyl)-4-[[(6R)-trans-2-carboxy-8-oxo-7-[(2,5-dichlorophenylthio)acetamido]-5-thia-1-azabicyclo[4.2.0]-oct-2-en-3-yl]methylthio]pyridinium chloride

HRID 3666Notes

Reaction equation

HRID 3666 reaction equation
[Cl-].[OH:2][CH:3]([CH2:38][NH:39]C(OC(C)(C)C)=O)[CH2:4][N+:5]1[CH:10]=[CH:9][C:8]([S:11][CH2:12][C:13]2[CH2:20][S:19][C@H:18]3[N:15]([C:16](=[O:34])[C@H:17]3[NH:21][C:22](=[O:33])[CH2:23][S:24][C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:26]=3[Cl:32])[C:14]=2[C:35]([OH:37])=[O:36])=[CH:7][CH:6]=1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl-:31].[OH:2][CH:3]([CH2:38][NH2:39])[CH2:4][N+:5]1[CH:6]=[CH:7][C:8]([S:11][CH2:12][C:13]2[CH2:20][S:19][C@H:18]3[N:15]([C:16](=[O:34])[C@H:17]3[NH:21][C:22](=[O:33])[CH2:23][S:24][C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:26]=3[Cl:32])[C:14]=2[C:35]([OH:37])=[O:36])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 867523491-(2-hydroxy-3-t-butoxycarbonylamino-1-propyl)-4-[[(6R)trans-2-carboxy-8-oxo-7-[(2,5-dichlorophenylthio)acetamido]-5-thia-1-azabicyclo[4.2.0]-oct-2-en-3-yl]methylthio]pyridinium chloride

Product 1

HCID 867523471-(2-Hydroxy-3-amino-1-propyl)-4-[[(6R)-trans-2-carboxy-8-oxo-7-[(2,5-dichlorophenylthio)acetamido]-5-thia-1-azabicyclo[4.2.0]-oct-2-en-3-yl]methylthio]pyridinium chlorideYield 127.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A slurry of 1-(2-hydroxy-3-t-butoxycarbonylamino-1-propyl)-4-[[(6R)trans-2-carboxy-8-oxo-7-[(2,5- dichlorophenylthio)acetamido]-5- thia-1-azabicyclo[4.2.0]-oct-2-en-3-yl]methylthio]pyridinium chloride (1.19 g, 1.58 mmol) in methylene chloride (22 mL) was cooled to 0° C. Anisole (3.4 mL) was added followed by trifluoroacetic acid (11 mL). The mixture was stirred for 30 min at 0° C. and 30 min at rt. The reaction mixture was concentrated in vacuo. The residue was stirred with ether until a yellow powder resulted. This solid was collected by filtration washing with ether. The crude product was stirred with ether (20 mL) for 45 min, and then the solid was collected by filtration. This was followed by similar treatments with acetone (1×10 mL) and then ether (1×20 mL). The final filtration gave 655 mg (54%) of the title compound as a yellow solid. 1H NMR (300 MHz, DMSO) δ2.80 (t, J=10, 1H), 3.06 (d, J=11, 1H), 3.31-3.44 (m, 1H), 3.60 (d, J=18, 1H), 3.90 (s, 2H), 4.10 (br s, 1H), 4.34-4.42 (m, 3H), 4.66 (d, J=12, 1H), 5.02 (d, J=5, 1H), 5.56 (t, J=6, 1H), 6.5-7.0 (br s, 1H), 7.21 (dd, J=2, 8, 1H), 7.41-7.46 (m, 2H), 8.12 (m, 2H), 8.30 (br s, 3H), 8.68 (m, 2H), 9.28 (m, 1H); MS (FIA) m/e 615 (MH+); Anal. calcd for C24H24 N4O5S3Cl2.HCl. HO2CCF3 : C, 40.71; H, 3.55; N, 7.30. Found: C, 40.70; H, 3.52; 7.38.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. stirringThe residue was stirred with ether until a yellow powder
  3. customresulted
  4. filtrationThis solid was collected by filtration
  5. washwashing with ether
  6. stirringThe crude product was stirred with ether (20 mL) for 45 min
  7. filtrationthe solid was collected by filtration
  8. filtrationThe final filtration

Sources & evidence

ORD record
ord-3e51c74c8ae2432e999cbab6081867a5
Source dataset
uspto-grants-1998_03
Patent number
US05734047

Reaction notes

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