Diethyl Ether → (S)-3-((R)-2-Ethyl-1-hydroxybutyl)pyrrolidine-1-carboxylic Acid t-Butyl Ester

Temperature

-78 °C

(S)-3-Formylpyrrolidine-1-carboxylic acid t-butyl ester (0.8 g, 3.8 mmol;) and THF (8 mL, 90 mmol) were combined under nitrogen, and the resulting solution was cooled to −78° C. 2M 3-Pentylmagnesium bromide in ether (4.70 mL, 9.4 mmol) was then added dropwise over 1 hour. The mixture was allowed to warm to room temperature slowly overnight. Then aqueous saturated NH4Cl (5 mL) was added dropwise to quench the reaction. The resulting mixture was extracted with EtOAc (2×25 mL), and the combined organic layers were washed with saturated aqueous NaHCO3 (25 mL) and saturated aqueous NaCl (25 mL), then dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (5-25% EtOAc in Hexanes) to yield the following as clear oils:

1. temperatureto warm to room temperature slowly overnight
2. customto quench
3. customthe reaction
4. extractionThe resulting mixture was extracted with EtOAc (2×25 mL)
5. washthe combined organic layers were washed with saturated aqueous NaHCO3 (25 mL) and saturated aqueous NaCl (25 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by flash chromatography (5-25% EtOAc in Hexanes)
10. customto yield the following as clear oils

ORD record

ord-4a7796a3182e48d3821234d80823f803

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09227933B2