4-Aminobenzoic Acid → HCID 136330138, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 4-carboxy-benzenediazonium chloride was prepared in the following way. Solid NaNO2 (345 mg, 5 mmol, 5 eq.) was added to a cooled suspension of 4-aminobenzoic acid (274 mg, 2 mmol, 2 eq.) in 6 M HCl (4 mL). The resulting mixture was stirred at 0° C. and turned into a slightly yellow-brownish solution. After 15 min the diazonium salt solution was slowly added to a solution of tyramine (137 mg, 1 mmol) in aqueous saturated bicarbonate. The pH of the reaction was kept basic by repeated addition of sodium bicarbonate. The mixture was allowed to slowly warm up to room temperature and was stirred overnight. Next, Fmoc-chloride (285 mg, 1.1 mmol, 1.1. eq) was added. After 1 h, the reaction was acidified with concentrated HCl. The formed solids were filtered and the filtrate was extracted with EtOAc, washed with water, dried over MgSO4 and concentrated under reduced pressure. Solids from extraction and filtration were combined and dry-loaded on a silica column, which was eluted with 0-10% MeOH in dichloromethane/acetic acid 99/1, yielding the title product as an orange-red solid (300 mg, 59% yield). The purity was sufficient for routine solid phase chemistry. An aliquot was further purified for analytical analysis. ESI-MS: 508.3 [M+H]+ 1H NMR (500 MHz, dmso-d6): δ 10.88 (s, 1H), 8.10 (d, 2H, J=8.6 Hz), 8.03 (d, 2H, J=8.6 Hz), 7.87 (d, 2H, J=7.6 Hz), 7.64 (d, 2H, J=7.2 Hz), 7.59 (d, 1H, J=1.8 Hz), 7.42-7.37 (m, 3H), 7.31-7.27 (m, 3H), 7.01 (d, 1H, J=8.4 Hz), 4.27 (d, 2H, J=7.1 Hz), 4.19 (t, 1H, J=7.0 Hz), 3.26-3.21 (m, 2H), 2.72 (t, 2H, J=6.8 Hz). HRMS: found [M+H]+ 508.1700. C30H26N3NaO5+ requires 508.1872.

Provenance & Evidence