4-[(tert-Butoxycarbonylamino)methyl]benzoic acid

Chemical Properties

white solid

Uses

4-(Boc-aminomethyl)benzoic Acid is the Boc protected form of 4-(Aminomethyl)benzoic Acid (A615230) and is used as a reagent in the synthesis of indoleamide derivatives as EP2 antagonists with high selectivity. 4-(Boc-aminomethyl)benzoic Acid is also used as a reagent in the synthesis of aminopyridine-derived amides as nicotinamide phosphoribosyltransferase inhibitors.

reaction suitability

reaction type: Boc solid-phase peptide synthesis

Synthesis

Phase 1 - Boc Protection: 4-(Aminomethyl)benzoic acid (10.00 g, 65.36 mmol) was stirred with di-tert-butyl dicarbonate (28.0 g, 130.72 mmol) in a solvent mixture of deionized water (100 mL) and tetrahydrofuran (100 mL) at room temperature. The reaction system was adjusted to pH ≈ 6 by slow addition of saturated aqueous sodium bicarbonate solution and the reaction was continuously stirred for 16 hours. Upon completion of the reaction, the reaction solution was carefully acidified to pH ≈ 3 with 1 M hydrochloric acid solution, at which time a white solid precipitated. The solid product was collected by filtration and washed with deionized water and dried to afford 4-[(tert-butoxycarbonylamino)methyl]benzoic acid as a white solid (16.1 g, 97% yield). Mass spectrometry analysis showed m/z = 274 [M + Na]+.

References

[1] Patent: WO2008/53131, 2008, A1. Location in patent: Page/Page column 58; 59-60
[2] Patent: WO2008/40934, 2008, A1. Location in patent: Page/Page column 57-58
[3] Patent: WO2010/20556, 2010, A1. Location in patent: Page/Page column 206
[4] Journal of Medicinal Chemistry, 2016, vol. 59, # 3, p. 965 - 984
[5] Journal of the Chemical Society - Perkin Transactions 1, 1999, # 4, p. 501 - 508