Hexamethylphosphoramide → HCID 79129082, compound

Temperature

-78 °C

To a solution of cyclobutanecarbonitrile (405 mg, 5 mmol) in THF (7 ml) was added 2.0M lithium diisopropylamide (2.5 ml, 5 mmol) dropwise at −78° C. The reaction solution was stirred at −78° C. for 40 minutes, followed by the addition of a solution of dihydrofuran-3(2H)-one (473 mg, 5.5 mmol) in hexamethylphosphoramide (268 mg, 1.5 mmol). The mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was quenched with 1N aqueous HCl solution and extracted with EtOAc (3×20 mL). The combined organic phases were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (eluted with petroleum ether:EtOAc=20:1) to provide the title compound as a corloless oil (0.37 g, yield 44%). 1H NMR (400 MHz, CDCl3): δ 4.15-4.05 (m, 2H), 3.86 (d, J=10.0 Hz, 1H), 3.74 (d, J=9.6 Hz, 1H), 2.47-2.42 (m, 4H), 2.39-2.31 (m, 3H), 2.01-1.94 (m, 2H).

1. temperatureThe mixture was warmed to room temperature
2. stirringstirred for 3 hours
3. customThe reaction mixture was quenched with 1N aqueous HCl solution
4. extractionextracted with EtOAc (3×20 mL)
5. washThe combined organic phases were washed with brine (10 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by column chromatography (eluted with petroleum ether:EtOAc=20:1)

ORD record

ord-7d617c31ee124ab7a779cc4bb2269702

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772500B2