4-(3-FORMYL-4-HYDROXYPHENYL)PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER Chemical Properties

Boiling point:

463.4±45.0 °C(Predicted)

Density 

1.225±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

10.42±0.35(Predicted)

4-(3-FORMYL-4-HYDROXYPHENYL)PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER Usage And Synthesis

Synthesis

General procedure: 5-bromo-2-hydroxybenzaldehyde (1000 g, 4.97 mol, 1 eq.) and tert-butyl 1-piperazinecarboxylate (1065.4 g, 5.72 mol, 1.1 eq.) were added to a reactor protected by nitrogen and palladium acetate (11.0 g, 0.049 mol, 0.01 eq.) and tri-tert-butylphosphine (10.0 g, 0.049 mol, 0.01 equiv) to a solution of toluene (0.3 L). Sodium tert-butoxide (1052.4 g, 10.9 mol, 2.2 eq.) was subsequently added. The reaction mixture was stirred at 42 °C for 22 h to form a reddish brown slurry. Upon completion of the reaction, a mixture of distilled water (8 L) and glacial acetic acid (800 mL) was added (pH adjusted to 5-6) and stirred for 10 min. The organic phase was separated and washed twice with distilled water (2 x 8L). The organic phase was dried by adding sodium sulfate (2.5 kg), stirred for 30 min and filtered. The dark orange organic phase was weighed (9.65 kg) and an aliquot (100 g) was concentrated under vacuum to give a dark orange oil. The oily substance was purified by column chromatography (silica gel, height: 30 cm, diameter: 4 cm, eluent: methyl tert-butyl ether/heptane 1:1) to afford the target compound tert-butyl 4-(3-formyl-4-hydroxyphenyl)piperazine-1-carboxylate as yellow crystals (8.9 g). The total yield was 56% based on an aliquot. Mass spectrum (ES+): 307 (M+H).

References

[1] Patent: EP2110374, 2009, A1. Location in patent: Page/Page column 30
[2] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 18, p. 4843 - 4852

4-(3-FORMYL-4-HYDROXYPHENYL)PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER(343306-50-3)Related Product Information

• 1-BOC-4-(4-HYDROXY-PHENYL)-PIPERAZINE
• TERT-BUTYL 4-(3-FORMYLBENZYL)TETRAHYDRO-1(2H)-PYRAZINECARBOXYLATE
• 4-(3-FORMYL-4-HYDROXYPHENYL)PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER