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

HRID 475813Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:13][CH2:12][CH2:11][C:10]1=[O:14].[C:15](Cl)([N:17]=[C:18]=[O:19])=[O:16].C1(C)C=CC=CC=1>C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:10]2[O:14][C:18](=[O:19])[NH:17][C:15](=[O:16])[C:11]=2[CH2:12][CH2:13]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an 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-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as brown solid. LC-MS (M+H)+=266.2. 1H NMR (500 MHz, CDCl3) δ ppm 8.19-8.64 (1H, m), 7.10 (1H, td, J=8.5, 6.3 Hz), 6.78-6.92 (2H, m), 4.36-4.49 (1H, m), 2.79-2.92 (1H, m), 2.59-2.78 (2H, m), 2.08 (1H, ddd, J=9.3, 6.9, 6.7 Hz).

Workup

washwashed with an 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-69642017129b4ddd8540a682a02be0fe
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637525B2

Reaction notes

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