1-Bromo-4-fluorobenzene → 1-Benzyl-4-(4-fluorophenyl)piperazine

HRID 343

Reaction equation

HRID 343 reaction equation
Fc1ccc(Br)cc1.c1ccc(CN2CCNCC2)cc1>CC(=O)O.CC(=O)O.CC(C)(C)[O-].CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.Cc1ccccc1.[Na+].[Pd]>Fc1ccc(N2CCN(Cc3ccccc3)CC2)cc1

Participants

7

Reactant 2

HCID 99931-Bromo-4-fluorobenzeneHCID 759941-Benzylpiperazine

Product 1

HCID 7631991-Benzyl-4-(4-fluorophenyl)piperazineYield 74.98%

Reagents, catalysts & solvents 4

HCID 23676156Sodium t-butoxideReagentHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 4144353Palladium (II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

diacetoxypalladium (12.74 mg, 0.06 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (32.8 mg, 0.06 mmol) were suspended in toluene (0.5 mL) under N2. Heated to 50C for 30 min (microwave). sodium 2-methylpropan-2-olate (109 mg, 1.13 mmol) was suspended in toluene (0.500 mL) under N2. 1-benzylpiperazine (0.099 mL, 0.57 mmol) and 1-bromo-4-fluorobenzene (0.093 mL, 0.85 mmol) were added, followed by the catalyst solution. Heated to 100C for 2h in the microwave (high abs), then rt over night. The product was purified on silica (0-25% EtOAc/heptane) Yield: 1-benzyl-4-(4-fluorophenyl)piperazine (115 mg, 75.0 %)

Sources & evidence

ORD record
ord-8809d217cb404d41bb5809dd5f95b269
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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