Diethyl Ether → (S)-tert-Butyl 3-((S)-1-hydroxy-3-methylbutyl)pyrrolidine-1-carboxylate

Temperature

-78 °C

(S)-3-Formylpyrrolidine-1-carboxylic acid t-butyl ester (6.0 g, 30.1 mmol) and THF (60 mL, 700 mmol) were combined under nitrogen, and the resulting solution was cooled to −78° C. 2.0M Isobutylmagnesium chloride in ether (18.1 mL, 36.1 mmol) was then added dropwise over 10 minutes. The mixture was allowed to warm to room temperature slowly overnight. Then aqueous saturated NH4Cl (100 mL) was added dropwise to quench the reaction. The resulting mixture was extracted with EtOAc (2×100 mL), and the combined organic layers were washed with saturated aqueous NaHCO3 (1×100 mL) and saturated aqueous NaCl (1×100 mL), then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography (80 g SiO2, ethyl ether) to yield (S)-3-((S)-1-hydroxy-3-methylbutyl)pyrrolidine-1-carboxylic acid t-butyl ester (1.6 g) and (S)-3-((R)-1-hydroxy-3-methylbutyl)pyrrolidine-1-carboxylic acid t-butyl ester (2.2 g) as oils.

1. temperatureto warm to room temperature slowly overnight
2. customto quench
3. customthe reaction
4. extractionThe resulting mixture was extracted with EtOAc (2×100 mL)
5. washthe combined organic layers were washed with saturated aqueous NaHCO3 (1×100 mL) and saturated aqueous NaCl (1×100 mL)
6. dry with materialdried over anhydrous MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by column chromatography (80 g SiO2, ethyl ether)

ORD record

ord-7c61b6c75feb4147b0e657352fac2523

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09227933B2