tert-Butanol → Tert-butyl 2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxy-3-methoxyphenyl)propanoate

Participants

Reaction Steps

t-BuOH (5.17 g, 6.67 mL, 69.8 mmol) was added to a stirred suspension of 2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxy-3-methoxyphenyl)propanoic acid (1.55 g, 4.98 mmol) in dry toluene (25 mL). The mixture was brought to reflux to give a homogeneous solution. N,N-dimethylformamide dineopentyl acetal (3.46 g, 4.17 mL, 15.0 mmol) was added dropwise over 1 h at reflux. After heating at reflux to 3-4 h, the reaction mixture was cooled to room temperature and a saturated solution of NaHCO3 (40 mL) was added. The mixture was extracted with CH2Cl2 (3×40 mL) and the combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Biotage Horizon, 40M, Si, ˜30 mL/min, 100% hexanes for 360 mL, gradient to 20% EtOAc in hexanes over 4536 mL) to afford tert-butyl 2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxy-3-methoxyphenyl)propanoate. Rf=0.42 (20% EtOAc/hexanes). LCMS calc.=390.2; found=389.9 (M+Na)+. 1H NMR (500 MHz, CDCl3): δ 6.82 (d, J=7.9 Hz, 1 H); 6.87-6.63 (m, 2 H); 5.54 (s, 1 H); 4.97 (d, J=7.8 Hz, 1 H); 4.40 (q, J=6.7 Hz, 1 H); 3.86 (s, 3 H); 2.98 (d, J=6.0 Hz, 2 H); 1.42 (s, 9 H); 1.41 (s, 9 H).

Provenance & Evidence