tert-Butyl 4-(4-bromopyridin-2-yl)piperazine-1-carboxylate

tert-Butyl 4-(4-bromopyridin-2-yl)piperazine-1-carboxylate Property

Boiling point:

442.8±45.0 °C(Predicted)

Density 

1.372±0.06 g/cm3(Predicted)

storage temp. 

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

pka

8.34±0.10(Predicted)

Appearance

White to off-white Solid

Safety

HS Code 

29333990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

tert-Butyl 4-(4-bromopyridin-2-yl)piperazine-1-carboxylate Chemical Properties,Usage,Production

Uses

tert-butyl 4-(4-bromopyridin-2-yl)piperazine-1-carboxylate is a useful reactant for the synthesis of sulfonyl fluorides from aryl bromides with the help of a palladium catalyst.

Synthesis

General procedure for the synthesis of tert-butyl 4-(4-bromopyridin-2-yl)piperazine-1-carboxylate from 4-bromo-2-fluoropyridine and N-BOC-piperazine: 1. 4-Bromo-2-fluoropyridine (1.55 g, 8.81 mmol), N-BOC-piperazine (2.46 g, 13.22 mmol) and potassium carbonate (3.65 g, 26.41 mmol) were suspended in dimethyl sulfoxide (10 mL) in a dry reactor. 2. The reaction mixture was transferred to a sealed tube, heated at 100 °C and stirred overnight. 3. Upon completion of the reaction, the mixture was cooled to room temperature and extracted by adding ethyl acetate and water. 4. The organic layer was separated, washed with brine and subsequently dried over anhydrous magnesium sulfate. 5. The solvent was evaporated under pressure to give the crude product. 6. Purification of the crude product by fast column chromatography (elution gradient: 100% hexane to 1:4 hexane/ethyl acetate) afforded the title compound tert-butyl 4-(4-bromopyridin-2-yl)piperazine-1-carboxylate (2.33 g, 78% yield) as a white solid. LRMS (m/z): 342/344 [M+1]+.

References

[1] Patent: WO2012/41476, 2012, A1. Location in patent: Page/Page column 60
[2] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 17, p. 5419 - 5423
[3] Patent: EP2441755, 2012, A1. Location in patent: Paragraph 0176
[4] Patent: EP2489663, 2012, A1. Location in patent: Paragraph 0095; 0096; 0097