Methyl iodide → methyl (2S)-4-hydroxypyrrolidine-2-carboxylate hydrochloride

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Reaction Steps

Iodomethane (573.0 mL, 9.20 mmol) was slowly added through a condenser at 0° C. To a suspension of trans-4-(2,4,6-trimethylbenzoyloxy) proline methyl ester (21 b, 1.35 g, 4.60 mmol) and triethylamine (1.29 mL, 9.20 mmol)in anhydrous methylene chloride (5 mL). The mixture was then refluxed overnight. Brine (20 mL) was then added to the mixture and the mixture was extracted with chloroform (30 mL 4X). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (1:1) to give 543.0 mg (32% yield from 4-hydroxyproline methyl ester hydrochloride salt) of the title compound (21c) as an oil. TLC Rf =0.65 (ethyl acetate:hexane=2:l). MS (DCl/NH3) m/e 306 (M+H)+. 1H NMR (CDCl3) δ: 6.85 (s, 2H, 2ArH), 5.44-5.52 (m, 1H, OCH), 3.77 (s, 3H, OCH3), 2.26-2.64 (m, 4H, 2CH2), 2.47 (s, 3H, NCH3), 2.30 (s, 6H, 2ARCH3), 2.28 (s, 3H, ARCH3).

Provenance & Evidence