Diphosgene → HCID 58615504, compound

HRID 2222962Notes

Reaction equation

HRID 2222962 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:31])[C@@H:12]([NH:20][C:21](=[O:30])[C@H:22]([NH2:29])[C:23]2[CH:28]=[CH:27][CH:26]=[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:41]=[C:42](Cl)OC(Cl)(Cl)Cl>O1CCCC1.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:31])[C@@H:12]([N:20]2[C:21](=[O:30])[C@@H:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[NH:29][C:42]2=[O:41])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4]

Participants

7

Reactant 3

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 86604046HCID 86604046, compound

Product 1

HCID 58615504HCID 58615504, compoundYield 28.1%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-[(S)-2-((R)-2-amino-2-phenyl-acetylamino)-3-phenyl-propionylamino]-thiazole-4-carboxylic acid methyl ester (0.795 g, 1.82 mmol) and diisopropylethylamine (1.10 mL, 6.2 mmol) in tetrahydrofuran (20 mL) was added to a solution of diphosgene (0.151 μL, 1.27 mmol) in a mixture of toluene (20 mL) and tetrahydrofuran (20 mL) over 10 minute at 0° C. The mixture was stirred at 0° C. for 20 minute then diluted with ethyl acetate. The mixture was washed with water, brine and dried over sodium sulfate. Evaporation of the solvents and purification of the residue by chromatography over silica gel gradient eluted between 0.2 and 1.2% v/v methanol in dichloromethane followed by recrystallization of the isolated product from acetonitrile gave 2-[(S)-2-((R)-2,5-dioxo-4-phenyl-imidazolidin-1-yl)-3-phenyl-propionylamino]-thiazole-4-carboxylic acid methyl ester as a white crystalline solid (166 mg, 20%).

Workup

  1. washThe mixture was washed with water, brine
  2. dry with materialdried over sodium sulfate
  3. customEvaporation of the solvents and purification of the residue by chromatography over silica gel gradient
  4. washeluted between 0.2 and 1.2% v/v methanol in dichloromethane
  5. customfollowed by recrystallization of the isolated product from acetonitrile

Sources & evidence

ORD record
ord-d19530a6803940aab6a0f259c9cfe30a
Source dataset
uspto-grants-2008_05
Patent number
US07371869B2

Reaction notes

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