p-Toluenesulfonic acid → (S,Z)-3-[(5-tert-Butyloxazol-4-yl)methylene]-6-benzylpiperazine-2,5-dione

HRID 15397Notes

Reaction equation

HRID 15397 reaction equation
[C:1]([C:5]1[O:9][CH:8]=[N:7][C:6]=1[CH:10]=[C:11](O)[C:12]([NH:14][C@H:15]([C:23](=[O:25])[NH2:24])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:13])([CH3:4])([CH3:3])[CH3:2].CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[C:1]([C:5]1[O:9][CH:8]=[N:7][C:6]=1/[CH:10]=[C:11]1/[C:12](=[O:13])[NH:14][C@@H:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:23](=[O:25])[NH:24]/1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 665902203-(5-tert-Butyloxazol-4-yl)-N-((S)-1-carbamoyl-2-phenylethyl)-2-hydroxyacrylamide

Product 1

HCID 11950454(S,Z)-3-[(5-tert-Butyloxazol-4-yl)methylene]-6-benzylpiperazine-2,5-dione

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Using a Dean-Stark trap whose trap part was filled with molecular sieves 3A, a solution of the compound from Example 7 (50 mg, 0.14 mmol) in toluene (20 mL) was refluxed in the presence of p-TsOH (0.8 mg, 0.0042 mmol) for 18 h. After removal of the solvent, the residue was purified by HPLC to obtain the title compound: yield 11.5 mg (23%), mp 52-56° C., 1H NMR (300 MHz, DMSO-d6) δ 10.65 (s, 1H), 8.60 (s, 1H), 8.47 (s, 1H), 7.24-7.13 (m, 5H), 6.37 (s, 1H), 4.52 (m, 1H), 3.20 (dd, J=3.7, 13.6 Hz, 1H), 2.95 (dd, J=5.0, 13.6 Hz, 1H), 1.31 (s, 9H); HRMS (EI): m/z 339.1584 (M+) (calcd for C19H21N3O3: 339.1583); [α]D25−128.9 (c=0.27, DMSO). Enantiomeric excess was determined to be 98% using chiral HPLC with a CHIRALCEL OD column.

Workup

  1. customAfter removal of the solvent
  2. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-0f79bf2c5fed4348be159ebf5c081ccb
Source dataset
uspto-grants-2010_06
Patent number
US07732605B2

Reaction notes

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