3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → (R)-tert-Butyl 3-(2-(1-(6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-5-fluoro-2-oxobenzo[d]oxazol-3(2H)-yl)ethyl)phenyl)-3-hydroxyazetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

In an oven-dried 25 mL RB flask, added (R)—N-(2,4-dimethoxybenzyl)-5-fluoro-3-(1-(2-iodophenyl)ethyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (32-1, 400 mg, 0.574 mmol) to THF (2154 μl) and cooled to −40° C. Was a suspension. Added isopropylmagnesium chloride-lithium chloride complex (1325 μl, 1.723 mmol) dropwise, stirred at −40° C. for 20 min—became a dark orange solution. Following this duration, added tert-butyl 3-oxoazetidine-1-carboxylate (32-2, 295 mg, 1.723 mmol) in THF (718 μl) dropwise via syringe. Solution turned yellow in color. After 60 min at −40° C., partitioned between 10 mL saturated NH4Cl+15 mL EtOAc, separated layers. Back-extracted aqueous with 2×10 mL EtOAc. Dried combined organics over Na2SO4, filtered, concentrated to give a yellow oil. Dissolved in 2 mL DMSO, purified by reverse-phase HPLC (C18 column, 10-90% (0.1% TFA/CH3CN:0.1% TFA/H2O) to give 32-3 as a white solid.

Provenance & Evidence