Diphosgene → (2S,3S)-N-(4-acetyl-thiazol-2-yl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyramide

HRID 32809

Reaction equation

[C:1]([C:4]1[N:5]=[C:6]([NH:9][C:10](=[O:33])[C@@H:11]([NH:20][C:21](=[O:32])[C@H:22]([NH2:31])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:13])[S:7][CH:8]=1)(=[O:3])[CH3:2].C(N(C(C)C)CC)(C)C.[O:43]=[C:44](Cl)OC(Cl)(Cl)Cl>O1CCCC1.C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:1]([C:4]1[N:5]=[C:6]([NH:9][C:10](=[O:33])[C@@H:11]([N:20]2[C:21](=[O:32])[C@@H:22]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[NH:31][C:44]2=[O:43])[C@H:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH3:13])[S:7][CH:8]=1)(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

(2S,3S)-N-(4-Acetyl-thiazol-2-yl)-2-[(R)-2-amino-2-(4-methoxy-phenyl)-acetylamino]-3-phenyl-butyramide (2.7 g, 90% purity, 5.2 mmol) and diisopropylethylamine (4.2 mL, 23.6 mmol) in tetrahydrofuran (50 mL) were added to a solution of diphosgene (0.48 mL, 4 mmol) in a mixture of toluene (50 mL) and tetrahydrofuran (50 mL) over 10 minutes at 0° C. The mixture was stirred at 0° C. for 20 minutes and diluted with ethyl acetate. The mixture was washed with water, brine and dried (sodium sulfate). Evaporation of the solvents and chromatography of the residue over silica gel with 0.4-1% v/v methanol in dichloromethane gave (2S,3S)-N-(4-acetyl-thiazol-2-yl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyramide (2.36 g, 92%) as a white solid.

Workup

washThe mixture was washed with water, brine
dry with materialdried (sodium sulfate)
customEvaporation of the solvents and chromatography of the residue over silica gel with 0.4-1% v/v methanol in dichloromethane

Sources & evidence

ORD record: ord-269506ebc9e54b1dac5e31a8e9d82d6e
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07427635B2

Linked notes

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