Hexamethylphosphoramide → HCID 79130368, 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. and the reaction solution was stirred at −78° C. for 40 minutes. A solution of dihydro-2H-pyran-4(3H)-one (550 mg, 5.5 mmol) in hexamethylphosphoramide (268 mg, 1.5 mmol) was added and the mixture was warmed up 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 obtain the title compound as a corloless oil (0.40 g, yield 44%). 1H NMR (400 MHz, CDCl3): δ 3.97 (dd, J=11.4, 4.2 Hz, 1H), 3.60-3.50 (m, 2H), 3.40-3.33 (m, 1H), 2.66-2.57 (m, 2H), 2.30-2.16 (m, 3H), 1.99-1.87 (m, 2H), 1.72 (dd, J=8.8, 3.6 Hz, 2H), 1.63-1.58 (m, 1H).

1. temperaturethe mixture was warmed up 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-2ca0ab5c25c3478f995628c1dc6333df

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772500B2