1-Bromo-3,5-difluorobenzene → methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate
Reaction equation
COC(=O)c1cc(C2CCCN2)c2oc(N3CCOCC3)cc(=O)c2c1.Fc1cc(F)cc(Br)c1>C1COCCO1.CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.CC1(C)c2cccc([PH+](c3ccccc3)c3ccccc3)c2Oc2c([PH+](c3ccccc3)c3ccccc3)cccc21.Fc1c[c-]cc(F)c1.O=C([O-])[O-].[Br][Pd+].[Cs+].[Cs+]>COC(=O)c1cc(C2CCCN2c2cc(F)cc(F)c2)c2oc(N3CCOCC3)cc(=O)c2c1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 100 °C
Procedure
Pd complexe (147 mg, 0.17 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (600 mg, 1.67 mmol), 1-bromo-3,5-difluorobenzene (0.241 ml, 2.09 mmol) and cesium carbonate (818 mg, 2.51 mmol) dissolved in 1,4-dioxane (12 ml). The resulting suspension was degased with argon and then stirred at 100 °C (15:00) for 18 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 0 to 6% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (314 mg, 39.9 %) as a clear yellow solid. **low yield but LCMS of the crude showed a nice reaction!** LCMS is OK.
Sources & evidence
- ORD record
- ord-d7d32d49e289422b9b8afc82aae7319c
- Source dataset
- 750 AstraZeneca ELN dataset
- Original link
- View source
Reaction notes
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