4-Piperidone → 1-(2-Chloro-4-fluorophenyl)piperidin-4-one

HRID 683Notes

Reaction equation

HRID 683 reaction equation
Fc1ccc(Br)c(Cl)c1.O=C1CCNCC1>CC(=O)O.CC(=O)O.CC(C)(C)[O-].CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1.Cc1ccccc1.[Na+].[Pd]>O=C1CCN(c2ccc(F)cc2Cl)CC1

Participants

7

Reactant 2

HCID 337214-PiperidoneHCID 27334061-Bromo-2-chloro-4-fluorobenzene

Product 1

HCID 290802911-(2-Chloro-4-fluorophenyl)piperidin-4-oneYield 0%

Reagents, catalysts & solvents 4

HCID 23676156Sodium t-butoxideReagentHCID 4144353Palladium (II) acetateCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a round bottom flask was added palladium(II) acetate (0.012 g, 0.06 mmol), dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.026 g, 0.06 mmol), and sodium tert-butoxide (0.213 g, 2.21 mmol). Added 5 mL toluene/t-butanol mix and purged with nitrogen. Added piperidin-4-one (0.15 g, 1.11 mmol), in 3 mL tol/tbuoh (slurry), followed by 1-bromo-2-chloro-4-fluorobenzene (0.255 g, 1.22 mmol), in 2 mL tol/tbuoh. Flushed with additional nitrogen and then heated to 120oC overnight. Let reaction mixture cool to room temperature and filtered through Celite. Rinsed repeatedly with EtOAc and concentrated in vacuo. Purified via ISCO 12g SiO2 column using 0-20% hexanes/ethyl acetate. Fractions 19 and 20 were combined and concentrated to afford a white solid. NMR (I200805922.42) shows a mess. Discarded. Will try another way.

Sources & evidence

ORD record
ord-5c5d7fac90d14102bcad7fe6bdad56a8
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Reaction notes

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