Trifluoroacetic acid → (R)-2-Hydroxy-4-phenylbutyric acid

Temperature

60 °C

Trifluoroacetic acid (40 mL) was added to a solution of N-tert-butoxycarbonyl-D-homophenylalanine (4.00 g) in dichloromethane (40 mL) at 0° C. After stirring at 0†° C. for 5 min and at room temperature for 40 min, the reaction mixture was evaporated in vacuo. The residue was dissolved in 10% sulfuric acid (80 mL), and the solution was warmed up to 60° C. After removing the bath, a solution of sodium nitrite (5.93 g) in water (5 mL) was added to the solution, and the solution was stirred at 60° C. for 7 hr. Then additional solution of sodium nitrite (1.98 g) in water (1.5 mL) was added, and the resulting solution was stirred at 60° C. for 2.5 hr. After cooling, urea (6.02 g) was added to the reaction mixture, and the whole was extracted with ethyl acetate. The extract was washed with saturated sodium hydrogen carbonate. The aqueous phase was acidified with 1 N hydrochloric acid, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and evaporated in vacuo to afford the title compound (2.51 g) as a white solid: 1H NMR (400 MHz, CDCl3) δ 1.92-2.10 (m, 1H), 2.10-2.27 (m, 1H), 2.80 (t, J=7.8 Hz, 2H), 4.20-4.32 (m, 1H), 5.12 (br s, 2H), and 7.12-7.40 (m, 5H).

1. waitat room temperature for 40 min
2. customthe reaction mixture was evaporated in vacuo
3. dissolutionThe residue was dissolved in 10% sulfuric acid (80 mL)
4. customAfter removing the bath
5. additiona solution of sodium nitrite (5.93 g) in water (5 mL) was added to the solution
6. stirringthe solution was stirred at 60° C. for 7 hr
7. additionThen additional solution of sodium nitrite (1.98 g) in water (1.5 mL) was added
8. stirringthe resulting solution was stirred at 60° C. for 2.5 hr
9. temperatureAfter cooling
10. additionurea (6.02 g) was added to the reaction mixture
11. extractionthe whole was extracted with ethyl acetate
12. washThe extract was washed with saturated sodium hydrogen carbonate
13. extractionextracted with ethyl acetate
14. washThe combined organic layers were washed with brine
15. dry with materialdried over anhydrous sodium sulfate
16. customevaporated in vacuo

ORD record

ord-e2b0740fad8c4cc2a2039498e4e2cf74

Source dataset

uspto-grants-2002_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06399629B1