3-Chlorophenol → HCID 54581864, compound

Participants

Reaction Steps

To a stirred solution of (2S,4R)-4-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (CAS Reg 74844-91-0) (6.1 kg, 24.87 mol), 3-chlorophenol (3.52 kg, 27.39 mol) & triphenylphosphine (7.18 kg, 27.37 mol) in tert-butyl methyl ether (30.5 L) at 0′C. was added diisopropylazodicarboxylate (5.53 kg, 27.35 mol) in tert-butyl methyl ether (15 L) dropwise. The mixture was stirred overnight at 20′C. The reaction was filtered and the liquors washed with 0.5M sodium hydroxide (aq) (2×12.5 L) & water (12.2 L). The tert-butyl methyl ether solvent was replaced with n-heptane (42.7 L) by atmospheric pressure distillation & cooled to crystallise crude product, which was collected by filtration (11.1 kg, 125% contaminated with ca 35% reduced diisopropyl dicarboxylate & triphenylphosphine oxide−corrected yield=86%).

Provenance & Evidence