Sulfuric Acid → Dimethyl 4-cyclopentyl-2-oxobutylphosphonate

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Reaction Steps

To a solution of dimethyl methylphosphonate (2.17 ml, 20 mmol) in anhydrous THF (20 mL), cooled at −78° C. was added n-BuLi (1.6 M in hexane, 13.7 mL, 22 mmol). The mixture was stirred for 30 minutes at this temperature under nitrogen. Methyl 3-cyclopentylpropanoate (1.56 g, 10 mmol), prepared from 3-cyclopentylpropionic acid (Aldrich) and methanol at the presence of the catalytic amount of the concentrated sulfuric acid (the procedure described in Intermediate 17.1), was added dropwise for 10 minutes. The mixture was stirred for 2 hours at −78° C., gradually was warm to room temperature. The mixture was quenched with addition of 1N HCl to pH 4-5. The organic layer was separated, washed with brine and dried over MgSO4. The residue was purified through flash chromatography on silica gel (EtOAc:Hexanes=1:1) to give the product (1.80 g) with colorless oil in 82% yield. 1HNMR (CD3OD, ppm) δ 1.03 (m, 2H), 1.51 (m, 1H), 1.61 (m, 6H), 1.73 (m, 2H), 2.63 (t, J=7.4 Hz, 2H), 3.09 (d, J=22.7 Hz, 2H), 3.76 (s, 3H), 3.87 (s, 3H)

Provenance & Evidence