tert-Butyldimethylsilane → HCID 58997402, compound

Participants

Reaction Conditions

Reaction Steps

The title B compound, (S)-2-t-butoxycarbonylamino-3-{4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-propionic acid benzyl ester (40 mg, 0.066 mmol) is dissolved in TFA (1.32 mL) containing t-butyidimethylsilane (0.033 mL, 0.198 mmol) in a 1 dram vial. The reaction is monitored by reverse phase HPLC (YMC CombiScreen Pro C18, 50×4.6 mm I.D., particle size S-5 micron, 12 nM) eluting at 3 mL/min with a gradient of 90:10 (0.1% TFA in water:MeCN) to 10:90 at 7.0 min. Starting material has a retention time of 4.97 min and a new peak has a retention time of 3.09 min, the starting material without the t-butoxylcarbonyl group as an “intermediate”, [M+H]+=510. After 25 min at RT, the reaction is heated at 80° C. for an additional 25 min. A new peak by HPLC has a retention time of 2.02 min, corresponding to the desired product. The reaction is cooled, filtered through florisil to remove a black precipitate and concentrated on a Savant Speedvac. The resulting residue is triturated with Et2O to give a white solid. This material is purified on a preparative reverse phase HPLC column (YMC CombiPrep Pro C18, 50×20 mm I.D., particle size S-5 micron, 12 nM) in two equal aliquots and eluted at 30 mL/min with a gradient of 90:10 (0.1% TFA in water:MeCN) 10:90 over 5.0 min, then held at 10:90 until 7 min. Fractions containing product are combined and concentrated on a Savant Speedvac to yield (S)-2-amino-3-[4-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-phenyl]-propionic acid benzyl ester as a white foam: [M−1]−=388.0.

Provenance & Evidence