3-Methoxy-dl-tyrosine → Tert-butyl 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoate

Participants

Reaction Steps

Prepared using General Procedure 1: To tert-butyl acetate (192 ml, 1435 mmol) was added finely ground 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoic acid (10.1 g, 47.8 mmol). The mixture was sonicated for 10 min to give a suspension. Trifluoromethanesulfonic acid (5.50 ml, 62.2 mmol) was added with stirring and the mixture was stirred overnight. The crude reaction was poured into a mixture of 2N NaOH (150 mL), brine (100 mL), ice (200 mL), and EA (100 mL) and basified to pH 9 with solid K2CO3. The mixture was filtered through celite and extracted with EA (2×100 mL). The organics were dried over MgSO4 and concentrated. The product residue was purified by chromatography (MeOH/DCM) to afford 4.75 g (37%) of tert-butyl 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoate INT-1. LCMS-ESI (m/z) calculated for C14H21NO4: 267; found 268 [M+H]+, tR=0.9 min (Method 4). 1H NMR (400 MHz, DMSO) δ 8.71 (s, 1H), 6.76-6.71 (d, J=1.9 Hz, 1H), 6.70-6.61 (m, 1H), 6.60-6.53 (m, 1H), 3.75-3.68 (s, 3H), 3.32 (s, 1H), 2.68 (m, 2H), 1.75 (s, 2H), 1.33 (s, 9H).

Provenance & Evidence