Potassium Carbonate → (5R)-3-{6-[(3,3-dimethyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinyl}-5-ethyl-5-methyl-2,4-imidazolidinedione

HRID 527717Notes

Reaction equation

[CH3:1][C:2]1([CH3:12])[C:6]2[C:7]([OH:11])=[CH:8][CH:9]=[CH:10][C:5]=2[CH2:4][O:3]1.Cl[C:14]1[N:19]=[CH:18][C:17]([N:20]2[C:24](=[O:25])[C@:23]([CH2:27][CH3:28])([CH3:26])[NH:22][C:21]2=[O:29])=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.C(OCC)(=O)C>[CH3:1][C:2]1([CH3:12])[C:6]2[C:7]([O:11][C:14]3[N:19]=[CH:18][C:17]([N:20]4[C:24](=[O:25])[C@:23]([CH2:27][CH3:28])([CH3:26])[NH:22][C:21]4=[O:29])=[CH:16][CH:15]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[CH2:4][O:3]1

Participants

Conditions

Temperature: 130 °C

Procedure

3,3-Dimethyl-1,3-dihydro-2-benzofuran-4-ol (Intermediate 193, 68 mg, 0.4 mmol) and (5R)-3-(6-chloropyridin-3-yl)-5-ethyl-5-methylimidazolidine-2,4-dione (Intermediate 194, 126 mg, 0.48 mmol) were dissolved in DMF (1.0 mL) and K2CO3 (143 mg, 1.03 mmol) was added. The resulting suspension was heated to 130° C. under microwave irradiation for 40 minutes. The reaction mixture was diluted with water (25 mL) and ethyl acetate (25 mL), and then two phases were separated. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash chromatography (Biotage system) on silica gel using cyclohexane/ethyl acetate 50:50 as eluent affording the title compound (70 mg) as a white solid.

Workup

customtwo phases were separated
washThe organic layer was washed with water and brine
dry with materialdried over Na2SO4
concentrationconcentrated under vacuum
customThe residue was purified by flash chromatography (Biotage system) on silica gel

Sources & evidence

ORD record: ord-1dc3d327d3c445d58faaf63d3440e725
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346790B2

Reaction notes

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