Diphosgene → HCID 57582930, compound

Participants

Reaction Steps

After cyclization of (R)-2-amino-2-(4-{[bis-(2-trimethylsilanyloxy-ethyl)-carbamoyl]-methoxy}-phenyl)-N-[(1S,2S)-1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propyl]-acetamide with diphosgene was complete and the reaction mixture had been partitioned between ethyl acetate and ice/water (as described in example 1, step 1-G) 1N aqueous hydrochloric acid (20 mL) was added to the ethyl acetate extracts and the mixture was stirred at ambient temperature for 15 minutes. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL) and washed with brine (50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by gradient flash chromatography using silica gel eluted with from 0 to 10% v/v methanol in dichloromethane. The product containing fractions were combined and concentrated to give a solid which was triturated with a 1:1 v/v mixture of dichloromethane/ether (1 mL). The suspension was stirred for 1 hour then filtered and dried to give N,N-bis-(2-hydroxy-ethyl)-2-(4-{(R)-1-[(1S,2S)-1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propyl]-2,5-dioxo-imidazolidin-4-yl}-phenoxy)-acetamide (30 mg, 27.7%).

Provenance & Evidence