Trifluoroacetic acid → HCID 51348416, compound

Participants

Reaction Conditions

Reaction Steps

To chloromethyl 1-(3-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)ureido)-2-methylpropan-2-yl carbonate (0.19 g, 0.348 mmol) in DMF (2 mL) are sequentially added triethylamine (0.048 mL, 0.348 mmol) and fumaric acid (0.020 g, 0.174 mmol) at RT. Contents heated at 70° C. (oil bath temp.) for 20 h. The reaction mixture was cooled to rt and subjected to prep. HPLC (Phenomex Luna AXIA 30×100 mm; 10 min. gradient; solvent A=10% CH3CN, 90% H2O, 0.1% TFA, solvent B=90% CH3CN, 10% H2O, 0.1% TFA). The desired fractions are collected and concentrated. The residue is partitioned between DCM (20 mL) and brine (10 mL). The DCM layer is dried over sodium sulfate and concentrated to yield (R,E)-3-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl)-2,8,8-trimethyl-5,10,14-trioxo-9,11,13-trioxa-4,6-diazaheptadec-15-en-17-oic acid (0.022 g, 0.035 mmol, 10.11% yield).

Provenance & Evidence