A mild and efficient one pot synthesis of 1,3,4-oxadiazoles from carboxylic acids and acyl hydrazides

Tetrahedron Letters

Volumn 47, Issue 28, 2006, Pages 4827-4830

  Rajapakse, Hemaka A ^a   Zhu, Hong ^a   Young, Mary Beth ^a   Mott, Bryan T ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

1,3,4 Oxadiazole; One pot; Synthesis

Indexed keywords

ACYLHYDRAZIDE; CARBOXYLIC ACID DERIVATIVE; HYDRAZIDE DERIVATIVE; OXADIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DEHYDRATION; DRUG SYNTHESIS; TECHNIQUE;

EID: 33744795751     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2006.05.051     Document Type: Article

References (13)

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10. 3P (116 mg, 0.441 mmol) were added in one portion. The dehydration step was allowed to proceed at 0 °C for 2 h and the reaction was poured onto a silica gel column for purification via normal phase chromatography (40 g silica, 30 mL/min, 5→50% EtOAc/hex) to afford the desired product 3 (66 mg, 0.18 mmol, yield 83%) as a white solid.
11. In comparison, coupling N-Boc-(l)-Phe-OH and benzoyl hydrazide with EDC, isolating the bis-acyl hydrazide and dehydrating under identical conditions provided 3 in 92% yield.
12. The reactions could be run in undried glassware under ambient atmosphere.
13. This reaction proceeded with ∼4% racemization as confirmed by chiral HPLC analysis (ChiralPak AD column, 60% EtOH/hex with 1 mL/L added diethylamine) of the individual enantiomers of 9. For a review detailing the challenges in the synthesis of and late stage manipulations involving aryl glycines, see:. Nicolaou K.C., Boddy C.N.C., Brase S., and Wissinger N. Angew. Chem., Int. Ed. 38 (1999) 2096