反应详情

To a solution of 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoic acid (for reference procedure see Example 18, WO2010/089107, which is incorporated herein by reference in its entirety) (0.2 g, 0.519 mmol), in dry DMF (6 ml), HATU (0.198 g, 0.521 mmol) and 4-methylmorpholine (0.057 ml, 0.521 mmol) were added and the mixture was stirred at RT until the complete conversion of the carboxylic acid into the activated ester occurred. 2-mercaptoacetic acid (0.030 ml, 0.434 mmol) was then added drop-wise, and the reaction mixture was stirred in the same conditions overnight. DMF was removed under reduced pressure and the crude was partitioned between EtOAc and HCl 1N; the organic layer was dried over Na2SO4, and the resulting crude was purified by trituration with Et2O affording 2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoylthio)acetic acid as an off-white solid containing some impurities (0.253 g, yield supposed to be quantitative, MS/ESI+ 459.7 [MH]+). The product was used for the next step without any further purification.

1. customDMF was removed under reduced pressure
2. customthe crude was partitioned between EtOAc and HCl 1N
3. dry with materialthe organic layer was dried over Na2SO4
4. customthe resulting crude was purified by trituration with Et2O