Hydrochloric Acid → 2-[3-(Tetrahydropyran-2-yloxy)-1-octynyl]-5-oxocyclopentaneheptanoic acid methyl ester

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Reaction Steps

Under a nitrogen atmosphere at -25° C, a solution of butyl lithium (50 ml of 2.2 molar solution in hexane) is added to a solution of 3-(tetrahydropyran-2-yloxy)-1-octyne {21.0 g, readily prepared from 1-octyn-3-ol (E. Crundwell, et al., J. Med. Chem., 8, 41 (1965)) and dihydropyran in the presence of conc. HCl} in toluene (25 ml). The mixture is stirred for 15 minutes and aluminum chloride (4.46 g) is added. After the reaction mixture has been stirred for an additional 45 minutes at -20° C, 5-oxo-1-cyclopentane-1-heptanoic acid methyl ester (11.2 g), described by J. Bagli and T. Bogri, Tetrahedron Letters, 3815 (1972) and U.S. Pat. No. 3,773,795, issued November 20, 1973, is added and the resultant mixture is allowed to come to room temperature (20°-25° C). The mixture is stirred for 16 hr. then diluted with saturated NH4Cl and extracted with ether. The ether extract is washed with saturated NH4Cl, water, dried and concentrated to yield an oily residue. Chromatography of the residue on silica gel using ethyl acetate-benzene (1:9) as eluant affords 2-[3-(tetrahydropyran-2-yloxy)-1-octynyl]-5-oxocyclopentaneheptanoic acid methyl ester (6; R1 = CH3 and R4 = tetrahydropyran-2-yl).

Provenance & Evidence