1-Methylpiperazine → 1-(4-Chloro-2-methoxyphenyl)-4-methylpiperazine

HRID 666Notes

Reaction equation

HRID 666 reaction equation
CN1CCNCC1.COc1cc(Cl)ccc1I>CC(=O)O.CC(=O)O.CC(C)(C)[O-].CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.Cc1ccccc1.[Na+].[Pd]>COc1cc(Cl)ccc1N1CCN(C)CC1

Participants

7

Reactant 2

HCID 531671-MethylpiperazineHCID 160792304-Chloro-1-iodo-2-methoxybenzene

Product 1

HCID 1190871951-(4-Chloro-2-methoxyphenyl)-4-methylpiperazineYield 63.57%

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
100 °C

Procedure

Palladium II acetate (25.09 mg, 0.11 mmol) was added to 4-chloro-1-iodo-2-methoxybenzene (300 mg, 1.12 mmol), 1-methylpiperazine (0.124 ml, 1.12 mmol), sodium 2-methylpropan-2-olate (215 mg, 2.23 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (323 mg, 0.56 mmol) in toluene (4 ml) at room temperture under nitrogen. The resulting mixture was stirred at 100oC overnight. The reaction mixture was filtered through celite and then concentrated under reduced pressure. The crude product was then taken up in DCM and washed with water. The crude product was purified by chromatography in DCM:MeOH 0-->10% to afford 1-(4-chloro-2-methoxyphenyl)-4-methylpiperazine (171 mg, 63.6 %) as yellow oil. This was carried through to the next reaction immediately as it is a controlled substance.

Sources & evidence

ORD record
ord-890c9e12800b48cca35bf6f2a67a4cca
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Reaction notes

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