An Optimised Synthesis of 2-[2,3-Bis(tert-butoxycarbonyl)guanidino]ethylamine

Shane M. Hickey; Trent D. Ashton; Simren K. Khosa; Frederick M. Pfeffer

doi:10.1055/s-0031-1290698

Synlett, Inhaltsverzeichnis

Synlett 2012; 23(12): 1779-1782
DOI: 10.1055/s-0031-1290698

letter

An Optimised Synthesis of 2-[2,3-Bis(tert-butoxycarbonyl)guanidino]ethylamine

Shane M. Hickey

Centre for Biotechnology, Chemistry and Systems Biology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia, Fax: +61(3)52271040 eMail: fred.pfeffer@deakin.edu.au

,

Trent D. Ashton

Centre for Biotechnology, Chemistry and Systems Biology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia, Fax: +61(3)52271040 eMail: fred.pfeffer@deakin.edu.au

,

Simren K. Khosa

Centre for Biotechnology, Chemistry and Systems Biology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia, Fax: +61(3)52271040 eMail: fred.pfeffer@deakin.edu.au

,

Frederick M. Pfeffer*

Centre for Biotechnology, Chemistry and Systems Biology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia, Fax: +61(3)52271040 eMail: fred.pfeffer@deakin.edu.au

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Abstract

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Abstract

This short report describes an improved, reliable, and high-yielding (>90%) synthesis of 2-[2,3-bis(tert-butoxycarbonyl)guanidino]ethylamine. The method is scalable (>5 g), and the product obtained directly from the reaction mixture requires no further purification. In addition, this methodology can be successfully applied to other diamine substrates (1,3-propyl and 1,4-butyl; 70% and 61% yield, respectively).

Key words

guanidine - synthesis - optimisation - cyclisation - protecting groups - NMR spectroscopy

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Referenzen

References and Notes
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20 2-[2,3-Bis( tert-butoxycarbonyl)guanidino]ethylamine (1) Boc-protected methylisothiourea 10 (5.81 g, 20.0 mmol) in CH₂Cl₂ (30 mL) was added in one portion to a stirred solution of 1,2-ethylenediamine (3.3 mL, 50.0 mmol) in CH₂Cl₂ (44 mL). The reaction was allowed to stir at 21 °C for 70 min. The reaction mixture was washed with H₂O (3 × 25 mL), brine (30 mL), then dried (MgSO₄) and filtered. Solvent was removed in vacuo at ambient temperature to afford 1 (5.37 g, 90%) as a white powder; mp 96.2–100.1 °C. ¹H NMR (270 MHz, CDCl₃): δ = 1.50 (9 H, br s, t-Bu), 1.51 (9 H, br s, t-Bu), 2.90 (2 H, t, J = 6.2 Hz, CH₂), 3.49 (2 H, app q, J_app = 5.5 Hz, CH₂), 8.67 (1 H, br s, NH), 11.51 (1 H, br s, NH). ¹³C NMR (67.5 MHz, CDCl₃): δ = 28.2, 28.4, 41.1, 43.5, 79.4, 83.2, 153.3, 156.5, 163.7. ESI-HRMS: m/z calcd for C₁₃H₂₆N₄O₄ [M + H]⁺: 303.2027; found: 303.2032
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