Isocyanatocarbonyl chloride → 7-(3,5-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione

HRID 2370169Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:13][CH2:12][CH2:11][C:10]2=[O:14])[CH:5]=[C:6]([F:8])[CH:7]=1.[C:15](Cl)([N:17]=[C:18]=[O:19])=[O:16]>C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:10]3[O:14][C:18](=[O:19])[NH:17][C:15](=[O:16])[C:11]=3[CH2:12][CH2:13]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 2-(3,5-difluorophenyl)cyclopentanone (4.765 g, 24.29 mmol) and carbonisocyanatidic chloride (4.61 g, 43.7 mmol) was heated at 58° C. for 1 h and at 130° C. for 2 h. Upon cooling to room temperature, the reaction mixture was dissolved in ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 7-(3,5-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (700 mg, 2.64 mmol, 10.87% yield). LC-MS (M+H)+=266.1. 1H NMR (500 MHz, CDCl3) δ ppm 8.79 (1H, br s), 6.68-6.86 (3H, m), 4.22 (1H, br s), 2.87 (1H, dt, J=7.0, 4.4 Hz), 2.63-2.82 (2H, m), 2.15 (1H, br s).

Workup

temperatureUpon cooling to room temperature
washwashed with saturated aqueous solution of sodium bicarbonate
customThe organic layer was separated
extractionthe aqueous layer was extracted with ethyl acetate
dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
filtrationfiltered
customThe solvent was removed in vacuum
customthe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record: ord-413af17ca2484f72b54f1665ce3d9a9c
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08710061B2

Reaction notes

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