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

HRID 41225

반응식

HRID 41225 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-857934d354314a05bbfb3f4c747ffead
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530470B2

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