Hydrochloric Acid → (S)-3-Hydroxy-1-(4-methylbenzyl)pyrrolidin-2-one

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Reaction Steps

HCl (4 M in 1,4-dioxane, 25.5 ml, 102 mmol) was added in one portion to a solution of (S)-3-((tert-butyldimethylsilyl)oxy)-1-(4-methylbenzyl)pyrrolidin-2-one (6.53 g, 20.4 mmol) in anyhdrous DCM (20.44 ml) at rt. A slight exotherm was noted. The reaction mixture was allowed to stir at rt for 2 h and then evaporated in vacuo. The residue was taken up in DCM (100 mL) and washed with a satd. sodium bicarbonate solution (100 mL) and brine (50 mL), and then the solution was dried over MgSO4 and concentrated to a residue. The crude product was purified by silica gel chromatography (120 g of silica) eluting with a gradient of 40% to 100% ethyl acetate in hexanes to provide 3.73 g (89%) of the desired product. LC/MS (Conditions B) RT=2.338 min, (M+H)+=206.2; 1H NMR (400 MHz, chloroform-d) δ 7.26-7.02 (m, 4H), 4.43 (d, J=3.5 Hz, 2H), 4.41-4.37 (m, 1H), 3.66 (d, J=2.6 Hz, 1H), 3.34-3.05 (m, 2H), 2.41 (dddd, J=12.8, 8.4, 6.6, 2.2 Hz, 1H), 2.34 (s, 3H), 1.93 (dq, J=12.8, 8.8 Hz, 1H).

Provenance & Evidence