1,3-DI-BOC-2-(TRIFLUOROMETHYLSULFONYL)GUANIDINE

Chemical Properties

White solid

Uses

1,3-Di-Boc-2-(trifluoromethylsulfonyl)guanidine is a guanidinylation reagent for amines and peptides.

Synthesis

N,N'-Bis(tert-butoxycarbonyl)guanidine (S6; 4.38 g, 16.9 mmol, 1.00 eq.) was dissolved in dichloromethane (CH2Cl2, 84.4 mL) at room temperature. The reaction mixture was cooled to -78°C and stirred for 10 minutes. Subsequently, freshly distilled triethylamine (Et3N; 1.79 g, 17.7 mmol, 1.05 eq.) was added slowly and dropwise. Trifluoromethanesulfonic anhydride (5.00 g, 17.7 mmol, 1.05 eq.) was added dropwise over 15 min at -78 °C while maintaining vigorous stirring. The reaction mixture was gradually warmed up to room temperature. After 6 hours of reaction, the reaction mixture was washed with 1.0 M potassium bisulfate (KHSO4) solution followed by water (H2O). The organic layers were combined, dried over anhydrous sodium sulfate (Na2SO4) and filtered. The solvent was removed by concentration under reduced pressure. Purification by silica gel fast column chromatography (eluent: 100% dichloromethane) afforded 1,3-di-BOC-2-(trifluoromethylsulfonyl)guanidine (S7; 5.51 g, 14.1 mmol, 83% yield) as a colorless solid.

References

[1] Journal of Organic Chemistry, 2001, vol. 66, # 3, p. 1038 - 1042
[2] Organic Syntheses, 2002, vol. 78, p. 91 - 91
[3] Journal of Organic Chemistry, 1998, vol. 63, # 12, p. 3804 - 3805
[4] Journal of Organic Chemistry, 1998, vol. 63, # 23, p. 8432 - 8439
[5] ChemMedChem, 2014, vol. 9, # 1, p. 129 - 150