Cesium carbonate → methyl 8-(1-(3-fluorophenyl)pyrrolidin-2-yl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate

HRID 41225

反応式

HRID 41225 の反応式
[CH3:1][C@@H:2]1[CH2:7][N:6]([C:8]2[O:9][C:10]3[C:15]([C:16](=[O:18])[CH:17]=2)=[CH:14][C:13]([C:19]([O:21][CH3:22])=[O:20])=[CH:12][C:11]=3[CH:23]2[CH2:27][CH2:26][CH2:25][NH:24]2)[CH2:5][CH2:4][O:3]1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Br[C:71]1[CH:76]=[CH:75][CH:74]=[C:73]([F:77])[CH:72]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(O[Pd]OC(=O)C)(=O)C>[F:77][C:73]1[CH:72]=[C:71]([N:24]2[CH2:25][CH2:26][CH2:27][CH:23]2[C:11]2[CH:12]=[C:13]([C:19]([O:21][CH3:22])=[O:20])[CH:14]=[C:15]3[C:10]=2[O:9][C:8]([N:6]2[CH2:5][CH2:4][O:3][C@H:2]([CH3:1])[CH2:7]2)=[CH:17][C:16]3=[O:18])[CH:76]=[CH:75][CH:74]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 140821-Bromo-3-fluorobenzeneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86672438methyl 2-((R)-2-methylmorpholino)-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate

生成物 1

HCID 86672444methyl 8-(1-(3-fluorophenyl)pyrrolidin-2-yl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate収率 64%

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
100 °C

実験手順

Diacetoxypalladium (8.44 mg, 0.04 mmol) was added to a stirred mixture of methyl 2-((R)-2-methylmorpholino)-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (0.35 g, 0.94 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.046 g, 0.08 mmol), 1-bromo-3-fluorobenzene (0.131 ml, 1.17 mmol) and cesium carbonate (0.459 g, 1.41 mmol) suspended in 1,4-dioxane (9 mL). The resulting suspension was degassed with argon and then stirred at 100° C. for 20 h. The reaction mixture was allowed to cool to room temperature, the insoluble were removed by filtration and the filtrate concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in EtAc. The solvents were evaporated to dryness to afford methyl 8-(1-(3-fluorophenyl)pyrrolidin-2-yl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate (0.279 g, 64%) as a beige foam. Mass Spectrum: m/z [M+H]+=467.

後処理

  1. customThe resulting suspension was degassed with argon
  2. temperatureto cool to room temperature
  3. customthe insoluble were removed by filtration
  4. concentrationthe filtrate concentrated
  5. custompurified by flash chromatography on silica gel eluting with 0 to 10% MeOH in EtAc
  6. customThe solvents were evaporated to dryness

出典と根拠

ORDレコード
ord-857934d354314a05bbfb3f4c747ffead
出典データセット
uspto-grants-2013_09
特許番号
US08530470B2

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