A convenient scalable one-pot conversion of esters and Weinreb amides to terminal alkynes

Tetrahedron Letters

Volumn 45, Issue 29, 2004, Pages 5597-5599

  Dickson, Hamilton D ^a   Smith, Stephon C ^a   Hinkle, Kevin W ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Alkynes; Bestmann Ohira; Seyferth Gilbert; Weinreb amides

Indexed keywords

ALDEHYDE; ALKYNE; AMIDE; ESTER; REAGENT;

ARTICLE; CHEMICAL REACTION; CHIRALITY; PROTON NUCLEAR MAGNETIC RESONANCE; REDUCTION; STEREOCHEMISTRY;

EID: 3042663278     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2004.05.139     Document Type: Article

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9. Typical large scale experimental procedure: ester f (27.0 g, 110 mmol) was dissolved in dichloromethane (100 mL), anhydrous toluene (300 mL) was added, and the solution cooled to -78°C. DIBAL-H (242 mL, 242 mmol, 1 M solution in toluene) was added via syringe over 45 min, and the mixture stirred for 4 h at -78°C. The reaction was monitored by TLC and judged to be complete after the starting ester was consumed. The mixture was quenched with anhydrous methanol (100 mL) at -78°C and allowed to warm to 0°C. The solvent volume was then reduced by approximately 50% under reduced pressure at 0°C. More MeOH (300 mL) was added followed by potassium carbonate (61.0 g, 220 mmol) and dropwise addition of the Bestmann-Ohira reagent (27.7 g, 143 mmol). The reaction was stirred to completion overnight at room temperature. Most of the solvent was removed, then ethyl acetate (800 mL) and Rochelle's salt (800 mL) was added. The mixture was stirred for 2 h and the organic layer was separated from the aqueous, washed with brine, dried over magnesium sulfate, and the solvent was removed under reduced pressure. The crude was purified with 50% ethyl acetate/hexane eluting the alkyne as a white solid (16.9 g, 72% yield)
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