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

HRID 41225

Reaction equation

HRID 41225 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-857934d354314a05bbfb3f4c747ffead
Source dataset
uspto-grants-2013_09
Patent number
US08530470B2

Linked notes

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