1,3-Dibromobutane → Racemic ethyl 1-(3-bromobutyl)cyclobutanecarboxylate

Temperature

-78 °C

To a 0° C. solution of DIPA (14.3 mL, 102 mmol) in THF (100 mL) was added n-BuLi (2.5M, 102 mmol). The Rx was stirred for 30-45 min then cooled to −78° C. Ethyl cyclobutane carboxylate (102 mmol, 1 equiv) was added slowly and the enolate was allowed to form for ˜30 min. At ˜78° C., above enolate was poured into 1,3-dibromobutane (2 equiv, 200 mmol) and Rx stirred at −78° C. for 1 h then warmed-up to RT. After 3 hours, NH4Cl was added and reaction extracted with EtOAc and washed with brine. The organic layer was dried over MgSO4, filtered and concentrated down to give 25 g of crude product. The residue was purified by silica gel chromatography (0% to 10% EtOAc in hexanes) to provide 11 g (42% yield) of racemic ethyl 1-(3-bromobutyl)cyclobutanecarboxylate 92.

1. customto form for ˜30 min
2. stirringstirred at −78° C. for 1 h
3. temperaturethen warmed-up to RT
4. waitAfter 3 hours
5. customreaction
6. extractionextracted with EtOAc
7. washwashed with brine
8. dry with materialThe organic layer was dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated down
11. customto give 25 g of crude product
12. customThe residue was purified by silica gel chromatography (0% to 10% EtOAc in hexanes)

ORD record

ord-4db428dcfce648909f29128a20c927f0

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859776B2