Imidazole → (S)-2-Iodomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

(S)-(−)-N-Boc-prolinol (10 g, 49.7 mmol), imidazole (6.76 g, 99.4 mmol) and triphenylphosphine (19.5 g, 74.5 mmol) were dissolved in diethyl ether (210 ml) and acetonitrile (80 ml) and the solution was cooled to 0° C. under an inert gas. Iodine (17.7 g, 70 mmol) was added in portions at this temperature. The yellow suspension was stirred for 15 h, and warmed to room temperature during this procedure. Addition of sodium thiosulfate solution (50 ml, 5 mol/l), stir for 5 min, the phases were separated. The aqueous phase was extracted with diethyl ether (2×100 ml) and the combined organic phases were washed with copper sulfate solution (30 ml, 5%) and sodium chloride solution (30 ml, saturated), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel) with hexane/diethyl ether (6:1). Yield: 10.57 g (68%)

1. stirringstir for 5 min
2. customthe phases were separated
3. extractionThe aqueous phase was extracted with diethyl ether (2×100 ml)
4. washthe combined organic phases were washed with copper sulfate solution (30 ml, 5%) and sodium chloride solution (30 ml, saturated)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by column chromatography (silica gel) with hexane/diethyl ether (6:1)

ORD record

ord-0f295c40050840b491727324fb348aeb

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08119805B2