1,4-Dibromobenzene → Tert-butyl 3-(4-bromophenyl)-3-hydroxypyrrolidine-1-carboxylate

Temperature

-78 °C

To a cold (−78° C.) solution of 1,4-dibromobenzene (3.89 g, 16.49 mmol) in tetrahydrofuran (80 mL) was added n-butyllithium (10.3 mL, 16.5 mmol, 1.6 M in hexane) dropwise. After 15 minutes, a solution of tert-butyl 3-oxopyrrolidine-1-carboxylate (3.05 g, 16.49, mmol) in tetrahydrofuran (10 mL) was added over 5 minutes. The reaction continued to stir at −78 °C. for 15 minutes and was then quenched by the addition of saturated NH4Cl (150 mL) and diethyl ether (150 mL). After warming to room temperature, the layers were separated, and the aqueous was extracted with additional diethyl ether (2×100 mL). The combined organic layers were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by MPLC (10% ethyl acetate in hexane to 50% ethyl acetate in hexane) to give the title product. MS (ESI) m/z 342 [M+H]+.

1. customwas then quenched by the addition of saturated NH4Cl (150 mL) and diethyl ether (150 mL)
2. temperatureAfter warming to room temperature
3. customthe layers were separated
4. extractionthe aqueous was extracted with additional diethyl ether (2×100 mL)
5. dry with materialThe combined organic layers were dried with anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by MPLC (10% ethyl acetate in hexane to 50% ethyl acetate in hexane)

ORD record

ord-014816244b3f4e0fb314679c72d698b6

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901152B2