Benzene, 4-bromo-1,2-dimethoxy- → tert-butyl (2R)-4-(3,4-dimethoxyphenyl)-2-propan-2-ylpiperazine-1-carboxylate

HRID 717

Reaction equation

HRID 717 reaction equation
CC(C)[C@@H]1CNCCN1C(=O)OC(C)(C)C.COc1ccc(Br)cc1OC>C1CCOC1.CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)[O-].[K+].[Pd]>COc1ccc(N2CCN(C(=O)OC(C)(C)C)[C@H](C(C)C)C2)cc1OC

Participants

7

Reactant 2

HCID 76114Benzene, 4-bromo-1,2-dimethoxy-HCID 24820392(R)-1-Boc-2-isopropylpiperazine

Product 1

HCID 69098812tert-butyl (2R)-4-(3,4-dimethoxyphenyl)-2-propan-2-ylpiperazine-1-carboxylateYield 90.52%

Reagents, catalysts & solvents 4

HCID 23665647Potassium tert-butoxideReagentHCID 83681Tris(1,1-dimethylethyl)phosphineCatalystHCID 2734558Bis(tri-tert-butylphosphine)palladium(0)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

22-Apr-09 09:56:23 +0100 4-bromo-1,2-dimethoxybenzene (0.068 mL, 0.46 mmol), (R)-tert-butyl 2-isopropylpiperazine-1-carboxylate (126 mg, 0.55 mmol) and BIS(TRI-T- BUTYLPHOSPHINE)PALLADIUM(0) (23.54 mg, 0.05 mmol) and potassium 2-methylpropan-2-olate (76 mg, 0.64 mmol) were suspended in THF (5 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 10 minutes in the microwave reactor and cooled to RT. LC-MS shows no starting material. The reaction mixture was filtered and the crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-tert-butyl 4-(3,4-dimethoxyphenyl)-2-isopropylpiperazine-1-carboxylate (152 mg, 91 %) as a yellow gum.

Sources & evidence

ORD record
ord-dcac8bcfa5124a8baee8e28e5e992678
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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