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

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).

1. temperatureThe mixture was then refluxed overnight
2. extractionthe mixture was extracted with chloroform (30 mL 4X)
3. washThe combined organic extracts were washed with brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (1:1)

ORD record

ord-fb3e8be47aa74b2f95183071c453376f

Source dataset

uspto-grants-1995_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05409946