Preparation and application of 2-bromobenzyl-N-succinimidyl carbonate_Industrial additives

Preparation and application background and overview of 2-bromobenzyl-N-succinimidyl carbonate

2-Bromobenzyl-N-succinimidyl carbonate is an organic intermediate that can be prepared in one step from 2-bromobenzyl alcohol and N,N’-disuccinimidyl carbonate.

Preparation and application of 2-bromobenzyl-N-succinimidyl carbonate

To a solution of 2-bromobenzyl alcohol (2.83 g, 15.0 mmol, 1.0 equiv) and DMAP (916 mg, 7.5 mmol, 0.5 equiv) in MeCN/DCM 1:1 (45 mL) was added N,N ‘-Disuccinimidyl carbonate (3.84 g, 15.0 mmol, 1.0 equiv). The mixture was continuously stirred at room temperature for 18 hours. The mixture was washed with H₂O (1×45mL), saturated NaHCO₃, sodium chloride solution (1×45mL), and washed with MgSO₄Dry, filter and concentrate in vacuo. The residue was recrystallized from iPrOH to give 2-bromobenzyl-N-succinimidyl carbonate. C12H10NO5Br, MW = 328.12. LC-MS 3: t_R = 0.82 min.

Preparation and application of 2-bromobenzyl-N-succinimidyl carbonate

2-Bromobenzyl-N-succinimidyl carbonate can be used to efficiently convert amines into protected guanidines.

Dissolve S-methylisothiourea sulfate (1.51 g, 5.43 mmol) in H₂O (16 ml) and add dioxane (14 mL) and 1M aqueous NaOH (11 mL, 11 mmol), then 2-bromobenzyl-N-succinimidyl carbonate (14.27 g, 43.5 mmol, 2 equiv) was added. The reaction mixture was stirred at room temperature for 24 hours, then concentrated under reduced pressure. The residue was dissolved in EtOAc (150 mL), and washed with 10% citric acid aqueous solution (3×30 ml) and saturated NaHCO₃ aqueous solution. , dried (MgSO₄) and evaporated, the solid residue was recrystallized from EtOH to give the product. Yield 7.42 g, 70%. Mp 101-103 °C. ¹H NMR (200 MHz, CD synthesis of fluorphlogopite Cl3): δ = 2.45 (s, 3 H), 5.29 (s, 2 H), 5.31 (s, 2 H), 7.15-7.61 (m, 8 H), 11.89 (s, 1 H). ^{13 Lithium metaborate}C NMR (50 MHz, CDCl₃): δ = 14.71, 67.43, 67.84, 122.93, 123.70, 127.54, 127.64, 129.34, 129.61, 130.28, 130.35, 132.77, 132.98, 134.01, 13 5.10, 151.35, 160.85, 173.25. Anal. Calcd for C18H16Br2N2O4S: C, 41.88; H, 3.12; N, 5.43; Br, 30.96. Found: C, 42.01; H, 3.01; N, 5.41; Br, 30.99.

References

[1] [Chinese invention, Chinese invention authorization] CN201180030390.1 1-phenyl-substituted heterocyclic derivatives and their use as prostaglandin D2 receptor modulators

[2] Gers T , Kunce D , Markowski P , et al. Reagents for Efficient Conversion of Amines to Guanidines. (p)[J]. Cheminform, 2010, 35(17).