(4-Carboxybutyl)triphenylphosphonium bromide → HCID 57857014, compound

Participants

Reaction Steps

4-Carboxybutyltriphenylphosphonium bromide (3.5 molar equivalents) is suspended in anhydrous THF under a nitrogen atmosphere. Potassium tert-butoxide in THF (1 M, 7 molar equivalents) is added dropwise to the white suspension. The reaction mixture becomes bright red over the course of the addition. The mixture continues stirring for 30 minutes at room temperature and is subsequently cooled to −15° C. in an ice/NaCl bath. The lactol ((3aR,4R,5R,6aS)-4-(3,3-difluoro-4-phenoxybutyl)-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-ol) (limiting reagent, prepared in Step F) is dissolved in THF and added dropwise to the ylide. The reaction mixture becomes lighter orange in color. The mixture continues stirring for 2 hours at −15° C. and is subsequently allowed to warm to room temperature and stir overnight as the reaction mixture becomes dark red. The reaction mixture is acidified with 5% KHSO4, diluted with brine (250 mL) and extracted with ethyl acetate (200 mL). The aqueous layer is extracted with another portion of ethyl acetate (50 mL) and the combined organic extracts are washed twice with brine (250 mL), dried over sodium sulfate and evaporated to yield crude product. The crude product is purified by flash chromatography on regular silica gel using ethyl acetate-hexane-acetic acid as eluent to afford the title intermediate.

Provenance & Evidence