Sodium hydride → 1-(Oxan-4-yl)imidazolidin-2-one

Temperature

-20 °C

A dry RB flask charged with 1-(2-chloroethyl)-3-(tetrahydro-2H-pyran-4-yl)urea (19.96 g, 97 mmol) in THF (480 mL), placed under Ar and stirred for 20 minutes at −20° C. after which 60% Sodium Hydride in mineral oil (9.66 g, 241 mmol) was added portion wise. The reaction was allowed to stir at −20° C. for 1 h and was then allowed to warm to ambient temp overnight. The reaction was cooled in an ice bath and quenched via slow addition of saturated NH4Cl (50 mL). Brine (30 mL) was added and the reaction was allowed to stir for 20 minutes. The organic layer was separated and aqueous layer extracted with EtOAc (2×) and THF (2×). The organic layers were combined, dried over anhydrous Na2SO4 and concentrated to dryness to afford a white gummy solid. The crude product was purified by silica gel chromatography (5% MeOH in CH2Cl2) to afford 1-(tetrahydro-2H-pyran-4-yl)imidazolidin-2-one as a white solid (10.54 g, 64% yield, 2 steps). 1H NMR (DMSO-d6): δ 6.24 (s, 1 H), 3.91-3.81 (m, 2 H), 3.73-3.61 (m, 1 H), 3.29-3.23 (m, 2 H), 3.22-3.21 (m, 2 H), 3.19-3.14 (m, 2 H), 1.67-1.53 (m, 2 H), 1.45-1.44 (m, 2 H); MS (ESI) m/z: 171.1 (M+H+).

1. additionwas added portion wise
2. temperatureto warm to ambient temp overnight
3. temperatureThe reaction was cooled in an ice bath
4. customquenched via slow addition of saturated NH4Cl (50 mL)
5. additionBrine (30 mL) was added
6. stirringto stir for 20 minutes
7. customThe organic layer was separated
8. extractionaqueous layer extracted with EtOAc (2×) and THF (2×)
9. dry with materialdried over anhydrous Na2SO4
10. concentrationconcentrated to dryness
11. customto afford a white gummy solid
12. customThe crude product was purified by silica gel chromatography (5% MeOH in CH2Cl2)

ORD record

ord-5b1c8d4b283944ec9c6fba0dd1c8c3e7

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133183B2