1-Bromo-3-fluorobenzene → Methyl 8-[1-(3-fluorophenyl)pyrrolidin-2-yl]-2-morpholin-4-yl-4-oxochromene-6-carboxylate

HRID 473

Reaction equation

HRID 473 reaction equation
COC(=O)c1cc(C2CCCN2)c2oc(N3CCOCC3)cc(=O)c2c1.Fc1cccc(Br)c1>C1COCCO1.CC(=O)O.CC(=O)O.CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.O=C([O-])[O-].[Cs+].[Cs+].[Pd]>COC(=O)c1cc(C2CCCN2c2cccc(F)c2)c2oc(N3CCOCC3)cc(=O)c2c1

Participants

7

Reactant 2

HCID 140821-Bromo-3-fluorobenzeneHCID 86672405methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate

Product 1

HCID 89051670Methyl 8-[1-(3-fluorophenyl)pyrrolidin-2-yl]-2-morpholin-4-yl-4-oxochromene-6-carboxylateYield 70.85%

Reagents, catalysts & solvents 4

HCID 10796Cesium carbonateReagentHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 4144353Palladium (II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

diacetoxypalladium (0.045 g, 0.20 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (1.8 g, 5.02 mmol), methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (1.8 g, 5.02 mmol) and cesium carbonate (2.455 g, 7.53 mmol) dissolved in 1,4-dioxane (35 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 11 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 20% methanol in ethyl acetate (on 50 min). The solvent was evaporated to dryness to afford methyl 8-(1-(3-fluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (1.610 g, 70.8 %) as a clear yellow foam.

Sources & evidence

ORD record
ord-5211120ee16b4ae79338b46c711839b3
Source dataset
750 AstraZeneca ELN dataset
Original link
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Linked notes

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