Hydrochloric Acid → Tyrosine Methyl Ester

To 3.30 g L-tyrosine (3A) suspended in 50 mL 2,2-dimethoxypropane, 5 mL of concentrated 36% HCl was added. The resulting mixture was stirred overnight at room temperature and then concentrated to dryness to afford crude methyl tyrosinate. 1H NMR (CDCl3, 500 MHz): δ 7.02 (d, J=8.5 Hz, 2H), 6.72 (d, J=8.5 Hz, 2H), 3.76-3.71 (m, 4H), 3.04 (dd, J1=13.8 Hz, J2=5.1 Hz, 1H), 2.82 (dd, J1=13.8 Hz, J2=7.7 Hz, 1H). The mixture was then dissolved in a 20 mL N,N-dimethylformamide solution containing 8.0 mL N,N-diisopropylethylamine. This solution was chilled in an ice-water bath, mixed with 4.78 g N-(benzyloxycarbonyloxy)succinimide in 10 mL N,N-dimethylformamide and stirred at room temperature for 3 hours before it was concentrated by rotary evaporation. The residue was dissolved in ethyl acetate and water, acidified to pH 3 and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous sodium sulfate and rotary evaporated to dryness. Flash column purification afforded a white solid (3B) in 4.65 g (78%). 1H NMR (CDCl3, 500 MHz): δ7.40-7.34 (m, 5H), 6.96 (d, J=7.8 Hz, 2H), 6.73 (d, J=7.8 Hz, 2H), 5.28 (s, 1H), 5.14 (d, J=12.4 Hz, 1H), 5.10 (d, J=12.4 Hz, 1H), 4.65 (m, 1H), 3.70 (s, 3H), 3.09 (dd, J1=13.8 Hz, J2=5.5 Hz, 1H), 3.02 (dd, J1=13.8 Hz, J2=5.7 Hz, 1H). 13C NMR (CDCl3, 500 MHz): δ172.2, 162.8, 155.7, 154.9, 136.2, 130.4, 128.6, 128.2, 128.1, 127.5, 115.5, 67.1, 55.0, 52.4, 37.5.

1. concentrationconcentrated to dryness

ORD record

ord-248d6c5403cf48d0838c5d6b37225397

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08445706B2