Cesium carbonate → HCID 86700658, compound

HRID 514878Notes

Reaction equation

[OH:1][C@H:2]1[CH2:6][CH2:5][NH:4][C:3]1=[O:7].Br[C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)[C:3]1=[O:7]

Participants

Conditions

Temperature: 80 °C

Procedure

To a 1,4-dioxane (20 mL) solution of (3S)-3-hydroxypyrrolidin-2-one (372 mg, 3.68 mmol) and 1-bromo-4-(trifluoromethyl)benzene (508 μL, 3.68 mmol) at room temperature was added 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (64 mg, 0.11 mmol), palladium(II) acetate (17 mg, 0.070 mmol) and cesium carbonate (1.80 g, 5.52 mmol). After stirring at 80° C. for 16 hours, the reaction mixture was allowed to cool down to room temperature and partitioned between diethyl ether (100 mL) and brine (100 mL). The organic layer was washed with brine (2×100 mL), dried (magnesium sulfate) and concentrated in vacuo to afford the crude product. Chromatography over silica gel, eluting with hexanes/ethyl acetate, afforded the title compound. 1H NMR (500 MHz, CDCl3) δ 7.81 (d, J=8.6 Hz, 2H), 7.64 (d, J=8.7 Hz, 2H), 4.52-4.48 (m, 1H), 3.89-3.77 (m, 2H), 3.05 (br s, 1H), 2.68-2.62 (m, 1H), 2.18-2.09 (m, 1H).

Workup

temperatureto cool down to room temperature
custompartitioned between diethyl ether (100 mL) and brine (100 mL)
washThe organic layer was washed with brine (2×100 mL)
dry with materialdried (magnesium sulfate)
concentrationconcentrated in vacuo
customto afford the crude product
washChromatography over silica gel, eluting with hexanes/ethyl acetate

Sources & evidence

ORD record: ord-0d0bee8ae832420a8df94b1192247e57
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108920B2

Reaction notes

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