Dichloromethane → (3R,5S)-1-t-Butoxycarbonyl-5-carboxy-3-methylpyrrolidine-2-one

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Reaction Steps

To a solution of (3R,5S)-1-t-butoxycarbonyl-5-hydroxymethyl-3-methylpyrrolidine-2-one in a solvent mixture of acetonitrile:carbon tetrachloride:water (2:2:3, 266 mL) was added sodium periodate (3 eq, 24.0 g) and ruthenium trichloride (2.2 mol %, 0.174 g). The solution was stirred 2 hr at room temperature and then diluted by the addition of dichloromethane (500 mL) and brine (200 mL). The organic phase was separated and the aqueous phase was extracted with dichloromethane (3 x 200 mL). The combined organic phases were dried over Na2SO4 then celite added. The solution was filtered under suction through a bed of celite and the filtrate was evaporated to give an oily residue which was crystallized in ethyl acetate and hexane to give 5.03 g product (54%). The mother liquor was purified by flash column chromatography on silica gel, eluting with 70% ethyl acetate in hexane (with 1% of formic acid) to give an additional 1.21 g (13%) of the acid (total 67% yield in two steps). 1H NMR (200 MHz, CDCl3): δ 6.65 (br s, 1H), 4.60 (d, J=8.6, 0.9 Hz, 1H), 2.70 (m, 1H), 2.40 (dd, J=12.5, 8.8 Hz, 1H), 2.0 (m, 1H), 1.55 (s, 9H), 1.25 (d, J=7.0 Hz, 3H).

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