Cesium carbonate → HCID 86672439, compound

HRID 41219Notes

Reaction equation

HRID 41219 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]=[C:75]([F:77])[CH:74]=[C:73]([F:78])[CH:72]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(O[Pd]OC(=O)C)(=O)C>[F:77][C:75]1[CH:76]=[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:72]=[C:73]([F:78])[CH:74]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 1363131-Bromo-3,5-difluorobenzeneHCID 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 86672439HCID 86672439, compoundYield 61%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

Diacetoxypalladium (4.58 mg, 0.02 mmol) was added to a stirred mixture of methyl 2-((R)-2-methylmorpholino)-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (190 mg, 0.51 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (25.09 mg, 0.04 mmol), 1-bromo-3,5-difluorobenzene (73.4 μl, 0.64 mmol) and cesium carbonate (249 mg, 0.77 mmol) suspended in 1,4-dioxane (5 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 6% MeOH in EtAc. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate (150 mg, 61%) as a beige foam.

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 6% MeOH in EtAc
  6. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-3dddf5a53c3449cbbef17517e6fdbb94
Source dataset
uspto-grants-2013_09
Patent number
US08530470B2

Reaction notes

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