Water → HCID 86604050, compound

HRID 2222967Notes

Reaction equation

HRID 2222967 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:36])[C@@H:12]([NH:20][C:21](=[O:35])[CH:22]([NH2:34])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][O:32][CH3:33])=[CH:25][CH:24]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4].C(N(C(C)C)CC)(C)C.[O:46]=[C:47](Cl)OC(Cl)(Cl)Cl.O>ClCCl>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:36])[C@@H:12]([N:20]2[C:21](=[O:35])[CH:22]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][O:32][CH3:33])=[CH:25][CH:24]=3)[NH:34][C:47]2=[O:46])[CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[S:8][CH:9]=1)=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 86604051HCID 86604051, compound

Product 1

HCID 86604050HCID 86604050, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-((S)-2-{2-amino-2-[4-(2-methoxy-ethoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester (a mixture of two epimers R/S=85:15) (0.16 g , 0.31 mmol) and diisopropylethylamine (0.31 mL, 1.78 mmol) in dichloromethane (20 mL) was added to a solution of diphosgene (0.03 μL, 0.25 mmol) in dichloromethane (30 mL) over a period of 10 minute at −10° C. The mixture was stirred at −10° C. for 15 minutes Water was added to quench the reaction, then the mixture was extracted with ethyl acetate. The organic layer was separated, washed with water, brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography over silica gel eluted with ethyl acetate to give 2-((S)-2-{4-[4-(2-methoxy-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester as a white solid (a mixture of two epimers R/S=85:15) (0.075 g, 87%).

Workup

  1. additionwas added
  2. customto quench
  3. customthe reaction
  4. extractionthe mixture was extracted with ethyl acetate
  5. customThe organic layer was separated
  6. washwashed with water, brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography over silica gel
  10. washeluted with ethyl acetate

Sources & evidence

ORD record
ord-522d534a33b74ab28c5e3503c3fa0f10
Source dataset
uspto-grants-2008_05
Patent number
US07371869B2

Reaction notes

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