p-Toluenesulfonic acid → HCID 24993089, compound

HRID 1673225Notes

Reaction equation

C([O:4][C@H:5]1[CH2:9][C:8](=[O:10])[N:7]([CH:11]2[C:20]3[C:15](=[N:16][C:17]([C:28]4[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=4[Cl:35])=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=4)[CH:19]=3)[O:14][C:13]([CH3:37])([CH3:36])[CH2:12]2)[C:6]1=[O:38])(=O)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([C:18]2[CH:19]=[C:20]3[CH:11]([N:7]4[C:8](=[O:10])[CH2:9][C@H:5]([OH:4])[C:6]4=[O:38])[CH2:12][C:13]([CH3:37])([CH3:36])[O:14][C:15]3=[N:16][C:17]=2[C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=2[Cl:35])=[CH:22][CH:23]=1

Participants

Conditions

Temperature: 85 °C

Procedure

The product of Step A (38 mg, 0.7 mmol) was dissolved in MeOH (2 mL) and p-toluenesulfonic acid (6 mg, 0.03 mmol) was added. The reaction was heated at 85° C. for 2 h and concentrated. The residue was dissolved in EtOAc and the solution was washed with saturated aq NaHCO3, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel gradient eluted with 0-60% EtOAc in hexane to afford the title compound. Further separation on an AD chiral column, eluting with 50% IPA/heptane, afforded the diastereomers: (LC-2) HPLC/MS (fast isomer on AD): 531.0 (M+1), 533.0 (M+3); Rt=3.58 min. (LC-2) HPLC/MS (slow isomer): 531.0 (M+1), 533.0 (M+3); Rt=3.59 min.

Workup

concentrationconcentrated
dissolutionThe residue was dissolved in EtOAc
washthe solution was washed with saturated aq NaHCO3
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography on silica gel gradient
washeluted with 0-60% EtOAc in hexane

Sources & evidence

ORD record: ord-76eeb8e0a6234c16bfcf74a9bbb595ab
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07999107B2

Reaction notes

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