Diphosgene → HCID 58615498, compound

HRID 2222952Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:34])[C@@H:12]([NH:20][C:21](=[O:33])[CH:22]([NH2:32])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([F:31])[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:44]=[C:45](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:34])[C@@H:12]([N:20]2[C:21](=[O:33])[CH:22]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([F:31])[CH:24]=3)[NH:32][C:45]2=[O:44])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-{(S)-2-[2-amino-2-(3-fluoro-4-methoxy-phenyl)-acetylamino]-3-phenyl-propionylamino}-thiazole-4-carboxylic acid methyl ester (0.335 g, 0.688 mmol) and diisopropylethylamine (0.48 mL, 2.75 mmol) in tetrahydrofuran (10 mL) was added to a solution of diphosgene (0.057 mL, 0.48 mmol) in a mixture of toluene (10 mL) and tetrahydrofuran (10 mL) over 10 minute at 0° C. The mixture was stirred at 0° C. for 15 minutes and 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 eluted with 3:97 methanol/dichloromethane gave 2-{(S)-2-[4-(3-fluoro-4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-propionylamino}-thiazole-4-carboxylic acid methyl ester (0.28 g, 79%).

Workup

washThe mixture was washed with water, brine
dry with materialdried over sodium sulfate
customEvaporation of the solvents and purification of the residue by chromatography over silica gel
washeluted with 3:97 methanol/dichloromethane

Sources & evidence

ORD record: ord-8914e159e6a24b44a3382335ae858d26
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07371869B2

Reaction notes

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