2-Chloroethyl isocyanate → HCID 90425773, compound

A 0° C. solution of 3-oxetanamine (0.200 g, 2.74 mmol) in THF (15 mL) was treated drop-wise with 2-chloroethyl isocyanate (0.257 mL, 3.01 mmol), allowed to warm to RT as the cooling bath expired, then concentrated to dryness. The residue was treated with toluene and concentrated to dryness (twice) to afford a white solid. The solid was dissolved in THF (15 mL), cooled to −20° C., under Ar, treated with NaH (60% in mineral oil, 0.274 g, 6.84 mmol), allowed to warm to RT and stirred overnight. The mixture was cooled to 0° C., quenched with satd. NH4Cl, warmed to RT, treated with brine and extracted with EtOAc (2×). The combined organics were dried over MgSO4 and concentrated to dryness. The aqueous layer was treated with solid NaCl until saturated, extracted with 1:1 EtOAc/THF (4×), then frozen and lyophilized. The lyophilized solid was stirred with EtOH for 1 h, the liquid decanted and the process repeated. The EtOH extracts were combined with the EtOAc/THF extracts, concentrated to dryness, then treated with 10% MeOH/DCM and the solids removed via filtration. The filtrate was combined with the initial EtOAc extracts and purified via silica gel chromatography (MeOH/DCM) to afford 1-(oxetan-3-yl)imidazolidin-2-one (270 mg, 69%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 6.52 (s, 1 H), 4.86 (m, 1 H), 4.71 (t, J=6.6 Hz, 2 H), 4.62 (t, J=7.2 Hz, 2 H), 3.58 (m, 2 H), 3.29 (m, 2 H); MS (ESI) m/z: 143.1 (M+H+).

1. concentrationconcentrated to dryness
2. additionThe residue was treated with toluene
3. concentrationconcentrated to dryness (twice)
4. customto afford a white solid
5. temperaturecooled to −20° C., under Ar
6. temperatureto warm to RT
7. temperatureThe mixture was cooled to 0° C.
8. customquenched with satd
9. temperatureNH4Cl, warmed to RT
10. additiontreated with brine
11. extractionextracted with EtOAc (2×)
12. dry with materialThe combined organics were dried over MgSO4
13. concentrationconcentrated to dryness
14. additionThe aqueous layer was treated with solid NaCl until saturated,
15. extractionextracted with 1:1 EtOAc/THF (4×)
16. temperaturefrozen
17. stirringThe lyophilized solid was stirred with EtOH for 1 h
18. customthe liquid decanted
19. concentrationconcentrated to dryness
20. additiontreated with 10% MeOH/DCM
21. customthe solids removed via filtration
22. custompurified via silica gel chromatography (MeOH/DCM)

ORD record

ord-473fb6a8726c4a59a8c8da82179c22fa

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133183B2