Benzyl Bromide → Ethyl 1-benzylcyclobutane-1-carboxylate

Temperature

0 °C

To a −78° C. solution of 2.8 mL (20.0 mmol) of diisopropylamine in 40 mL of dry tetrahydrofuran was added 13.75 mL (22 mmol) of 1.6 M n-butyllithium in hexanes. The reaction was let warm to 0° C. and then cooled to −78° C. A solution of 2.7 mL (20 mmol) of ethyl cyclobutanecarboxylate in 10 mL of tetrahydrofuran was added dropwise and the reaction let warm to 0° C. The reaction was stirred for 15 min before being cooled to −78° C. To the solution was added 3.1 mL (26 mmol) of benzyl bromide dropwise and the reaction stirred for 15 min before being let warm to room temperature and stirred overnight. The reaction was quenched with water and extracted with ethyl acetate. The organic phase was washed with saturated ammonium chloride, washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to afford 5.24 g of crude ethyl 1-benzylcyclobutanecarboxylate. The crude product was dissolved in 100 mL of tetrahydrofuran and cooled to 0° C. To this solution was added dropwise 14.1 mL (14.1 mmol) of 1M lithium aluminum hydride in tetrahydrofuran. The reaction was stirred for 1 h before being carefully quenched with brine. The mixture was filtered through a celite plug and the filter cake washed with ethyl acetate. The filtrate was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to afford 1.6 g (45%) of ethyl (1-benzylcyclobutyl)methanol. 1H NMR (300 MHz, DMSO-d6) δ 7.18-7.34 (m, 5H), 4.63 (t, J=5 Hz, 1H), 3.24-3.25 (d, J=5H, 2H), 2.71 (s, 2H), 1.66-1.79 (m, 6H).

1. temperaturecooled to −78° C
2. temperaturethe reaction let warm to 0° C
3. temperaturebefore being cooled to −78° C
4. stirringthe reaction stirred for 15 min
5. temperaturebefore being let warm to room temperature
6. stirringstirred overnight
7. customThe reaction was quenched with water
8. extractionextracted with ethyl acetate
9. washThe organic phase was washed with saturated ammonium chloride
10. washwashed with brine
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated under reduced pressure

ORD record

ord-4ff76035953a4e3cb3a7318331d8ffb2

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07282512B2