1-Cbz-4-hydroxymethylpiperidine Chemical Properties

Boiling point:

396.4±25.0 °C(Predicted)

Density 

1.162±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

14.94±0.10(Predicted)

Appearance

Colorless to off-white Solid-liquid mixture

CAS DataBase Reference

122860-33-7(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36/37/39-37/39

HS Code 

2933399990

1-Cbz-4-hydroxymethylpiperidine Usage And Synthesis

Uses

1-N-Cbz-hydroxymethyl-piperidine is an intermediate used in the synthesis of benzoyloxyethylpiperidinylmethylamine as fluorescent antagonists for human 5-HT4 receptors. It is also used to prepare diaminobutane derivatives as potent Ca2+-Permeable AMPA receptor antagonists.

Synthesis

General procedure for the synthesis of N-CBZ-4-piperidinemethanol (1-CBZ-4-hydroxymethylpiperidine) from 4-(hydroxymethyl)piperidine and benzyl chloroformate: 4-(hydroxymethyl)piperidine (2.0 g, 17.4 mmol) was dissolved in anhydrous dichloromethane (DCM, 100 mL), and the solution was cooled to 0 °C and stirred. Triethylamine (4.8 mL, 34.8 mmol) and benzyl chloroformate (3.7 mL, 34.8 mmol) were added sequentially, then the reaction mixture was slowly warmed to room temperature and stirring was continued for 2 hours. Upon completion of the reaction, the mixture was transferred to a partition funnel and layered with DCM (50 mL) and water (30 mL). The organic phase was separated and the aqueous phase was extracted with DCM (2 x 50 mL). All organic phases were combined, washed once with brine (30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography using a gradient elution with hexane/EtOAc (70% to 100%) to afford 3.85 g (89% yield) of N-benzyloxycarbonyl-4-(hydroxymethyl)piperidine (E-12) as a clear oil. Its 1H NMR (CDCl3) data were as follows: δ 1.17 (m, 2H), 1.72 (m, 3H), 2.15 (br s, 1H), 2.78 (t, 2H, J = 12 Hz), 3.47 (d, 2H, J = 6.04 Hz), 4.20 (d, 2H, J = 11.68 Hz), 5.12 (s, 2H), 7.33 (m , 5H).

References

[1] Patent: WO2005/80394, 2005, A1. Location in patent: Page/Page column 131
[2] European Journal of Organic Chemistry, 2008, # 25, p. 4277 - 4295
[3] Patent: WO2010/46780, 2010, A2. Location in patent: Page/Page column 63-64
[4] Journal of the American Chemical Society, 2017, vol. 139, # 24, p. 8110 - 8113
[5] Patent: US2003/55244, 2003, A1

1-Cbz-4-hydroxymethylpiperidine(122860-33-7)Related Product Information

• Benzyl alcohol
• 2,2,6,6-Tetramethyl-4-piperidinol
• Tris(hydroxymethyl)nitromethane
• Benzyloxyacetyl chloride
• Benzyl isocyanate
• Benzyl chloride
• 2-Hydroxyethyl methacrylate
• Benzyl benzoate
• Benzyl nicotinate
• Trimethylolpropane
• 2,2,6,6-Tetramethylpiperidinooxy
• Trimethoprim
• CARBOXYMETHYLCELLULOSE SODIUM SALT
• 4-Piperidinemethanol
• N-Cbz-3-hydroxymethylpiperidine
• Carbamic acid, [(1R)-1-(3-bromophenyl)-2-hydroxyethyl]-, 1,1-dimethylethyl ester (9CI)
• Tris(hydroxymethyl)aminomethane
• 1-N-CBZ-NIPECOTAMIDE