N-Boc-piperidine-2-methanol

Chemical Properties

Solid

Uses

Reactant for:

• Julia coupling for synthesis of corydendramine A
• Cyclization-functionalization of nitrogen-containing dienes

Reactant for synthesis of:

• Heterocyclic compounds
• Anthranilamide inhibitors of factor Xa
• Human GnRH receptor antagonists
• Sphingosine-1-phosphate receptor agonists

Synthesis

The general procedure for the synthesis of 1-Boc-2-piperidinemethanol from di-tert-butyl dicarbonate and 2-piperidinemethanol is as follows: 1. 2-Piperidinemethanol (3.0 g, 25.60 mmol) was dissolved in dichloromethane (DCM, 100 mL) under stirring. 2. triethylamine (14.5 mL, 91.08 mmol) was added to the above solution in batches, followed by di-tert-butyl dicarbonate (7.2 g, 31.0 mmol). 3. The reaction mixture was stirred at room temperature for 16 hours. 4. Upon completion of the reaction, water (70 mL) was added for stratification to separate the organic layer. 5. The organic layer was washed with water (2 x 50 mL) and then dried with anhydrous sodium sulfate (Na2SO4). 6. The dried organic layer was filtered and concentrated under vacuum to give 1-Boc-2-piperidinemethanol (6.0 g, quantitatively) as a light brown oil, which can be used without further purification. The nuclear magnetic resonance hydrogen spectrum (1H NMR, CDCl3) data were as follows: δ 4.42-4.22 (1H, m), 4.05-3.91 (1H, m), 3.89-3.77 (1H, m), 3.71-3.53 (1H, m), 2.97-2.81 (1H, m), 2.32-2.08 (1H, m), 1.90 (1H, s ), 1.77-1.57 (3H, m), 1.54 (1H, s), 1.52-1.38 (10H, m).

References

[1] Patent: WO2007/141504, 2007, A1. Location in patent: Page/Page column 57
[2] Organic Letters, 1999, vol. 1, # 4, p. 667 - 670
[3] Journal of Organic Chemistry, 1996, vol. 61, # 17, p. 6040 - 6043
[4] Tetrahedron Asymmetry, 1998, vol. 9, # 11, p. 1951 - 1965
[5] Tetrahedron Letters, 2015, vol. 56, # 46, p. 6478 - 6483