Cesium carbonate → (3S)-3-hydroxy-1-[4-(trifluoromethyl)phenyl]pyrrolidin-2-one

HRID 514878ノート

反応式

HRID 514878 の反応式
[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]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 11029774(3S)-3-hydroxypyrrolidin-2-one

生成物 1

HCID 86700658(3S)-3-hydroxy-1-[4-(trifluoromethyl)phenyl]pyrrolidin-2-one

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-0d0bee8ae832420a8df94b1192247e57
出典データセット
uspto-grants-2015_08
特許番号
US09108920B2

反応ノート

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