p-Toluenesulfonic acid → L-Tyrosine

The para-toluenesulfonic acid salt of tyrosine benzyl ester (5.05 g, 11.4 mmol) was dissolved in THF (50 mL) containing DIEA (2.18 mL, 12.5 mmol) and di-tert-butyidicarbonate (2.98 g, 13.7 mmol) was added in one portion. The reaction was stirred 1.5 h at room temperature. Volatiles were removed under reduced pressure and the residue was dissolved in Et2O (150 mL). The solution was washed successively with water (25 mL), 5% citric acid (25 mL) and 5% NaHCO3 (25 mL). After drying (MgSO4), the solvent was evaporated under reduced pressure and the residue dissolved in acetone (100 mL). Cesium carbonate (4.83 g, 14.8 mmol) and methyl bromoacetate (1.3 mL, 13.7 mmol) were added and the heterogeneous mixture was stirred overnight at room temperature. Solids were then removed by filtration (acetone for washings) and the filtrate evaporated. The residue was dissolved in Et2O (150 mL) and washed with water (25 mL) and brine (25 mL). After drying (MgSO4), the solution was concentrated and the residue purified by flash chromatography using 25-50% EtOAc/hexane as eluent. The fully protected tyrosine derivative was obtained as a colorless oil (3.61 g).

1. additionwas added in one portion
2. customVolatiles were removed under reduced pressure
3. dissolutionthe residue was dissolved in Et2O (150 mL)
4. washThe solution was washed successively with water (25 mL), 5% citric acid (25 mL) and 5% NaHCO3 (25 mL)
5. dry with materialAfter drying (MgSO4)
6. customthe solvent was evaporated under reduced pressure
7. dissolutionthe residue dissolved in acetone (100 mL)
8. stirringthe heterogeneous mixture was stirred overnight at room temperature
9. customSolids were then removed by filtration (acetone for washings)
10. customthe filtrate evaporated
11. dissolutionThe residue was dissolved in Et2O (150 mL)
12. washwashed with water (25 mL) and brine (25 mL)
13. dry with materialAfter drying (MgSO4)
14. concentrationthe solution was concentrated
15. customthe residue purified by flash chromatography

ORD 기록

ord-18db573d8e324bb38d3060ded58b676d

출처 데이터셋

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07439258B2