Ethyl bromoacetate → Tert-butyl 3-(2-ethoxy-2-oxoethyl)-2-oxopyrrolidine-1-carboxylate

Temperature

-78 °C

tert-Butyl 2-oxopyrrolidine-1-carboxylate (10 g, 54.0 mmol) was dissolved in THF (75 mL) and cooled to −78° C. LDA (1.8 M in THF/heptane, 30.0 mL, 54.0 mmol) was added and the solution was stirred for 1 h. Ethyl 2-bromoacetate (9.02 g, 54.0 mmol) was added and the mixture was stirred for 1 h and allowed to warm to room temperature and stirred for 16 h. The reaction mixture was partitioned between water and EtOAc. The aqueous layer was extracted two times with EtOAc and the combined extracts were dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by column chromatography to provide partially purified tert-butyl 3-(2-ethoxy-2-oxoethyl)-2-oxopyrrolidine-1-carboxylate. tert-Butyl 3-(2-ethoxy-2-oxoethyl)-2-oxopyrrolidine-1-carboxylate (4.72 g, 17.40 mmol) was dissolved in EtOH (30 mL) and TFA (10 mL). The reaction was stirred at room temperature for 2 h and 20 mL of TFA was added. After stirring for an additional 2 h, the reaction mixture was concentrated under reduced pressure and purified by column chromatography to provide the title compound (1.77 g). 1H NMR (400 MHz, CDCl3) δ ppm 1.26 (t, J=7.2 Hz, 3H), 1.81-1.93 (m, 1H), 2.35-2.49 (m, 2H), 2.75-2.85 (m, 1H), 2.88 (dd, J=16.4, 3.9 Hz, 1H), 3.31-3.40 (m, 2H), 4.09-4.21 (m, 2H), 5.96 (bs, 1H).

1. stirringthe mixture was stirred for 1 h
2. temperatureto warm to room temperature
3. stirringstirred for 16 h
4. customThe reaction mixture was partitioned between water and EtOAc
5. extractionThe aqueous layer was extracted two times with EtOAc
6. dry with materialthe combined extracts were dried (sodium sulfate)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by column chromatography

ORD record

ord-060175ec7ab241259354f6c8fa0c1bb3

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108969B2