Sodium Iodide → [tert-Butoxycarbonylmethyl-(2-hydroxy-phenyl)-amino]-acetic acid tert-butyl ester

Participants

Reaction Steps

A solution of 2-aminophenol (10) (5.0 g, 45.8 mmol) and NaI (3.44 g, 23 mmol) in dry CH3CN (150 mL) was treated with 1,8-bis(dimethylamino) naphthalene (21.6 g, 100.8 mmol) followed by t-butyl bromoacetate (14.2 mL, 96.2 mmol) under an Ar atmosphere and stirred at reflux overnight. After the mixture was cooled to room temperature, the precipitated salts were filtered off and washed with additional EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography, eluting with CH2Cl2/hexane/EtOAc=1:4:0.2 to yield 12.3 g (80%) of the desired product (11) as a light yellow oil. Rf=0.3 (in CH2Cl2/hexane/EtOAc=1:4:0.2); 1H NMR (300 MHz, CDCl3) δ 7.29 (dd, 7.9 and 1.5 Hz, 1H), 7.07 (m, 1H), 6.94 (dd, 8.1 and 1.5 Hz, 1H), 6.79 (m, 1H), 5.30 (s, 1H), 3.74 (s, 4H), 1.46 (s, 18H); 13C NMR (75 MHz, CDCl3) δ 171.2, 153.6, 137.4, 127.3, 126.0, 119.9, 115.6, 81.9, 57.0, 28.0; mass spectrum, calculated for C18H27NO5 (MH+) 338.2, Found 337.9.

Provenance & Evidence