Reaction #11008

Reaction equation

t-butyl methyl ether

L-Phenylalanine

sulfuric acid

sodium nitrite

→

(2S)-2-hydroxy-3-phenylpropionic acid

Yield 86.0%

Solvents

water

water

Conditions

Workup

1. 1
   workup.ADDITIONwas added over 5 hours
2. 2
   workup.ADDITIONAfter addition
3. 3
   workup.STIRRINGof stirring at 20° C.
4. 4
   Otherthe organic phase was separated
5. 5
   Extraction(extract 1)
6. 6
   workup.ADDITIONFurther, 50 ml of t-butyl methyl ether was added to the aqueous phase
7. 7
   workup.STIRRINGthe mixture was stirred at 20° C. for 30 minutes
8. 8
   Otherthe organic phase was separated
9. 9
   Extraction(extract 2)
10. 10
    ExtractionThe combined extract (116.5 g)

Procedure

L-Phenylalanine (10.00 g, 60.5 mmol) was added to a dilution of 8.88 g (90.5 mmol) of concentrated sulfuric acid in 110 g of water and then, at an inside temperature of 20° C., a mixture of 10.45 g (151.5 mmol) of sodium nitrite and 20 g of water was added over 5 hours. After addition, the mixture was stirred at 20° C. for 20 hours, 100 ml of t-butyl methyl ether was then added and, after 30 minutes of stirring at 20° C., the organic phase was separated (extract 1). Further, 50 ml of t-butyl methyl ether was added to the aqueous phase, the mixture was stirred at 20° C. for 30 minutes, and the organic phase was separated (extract 2). The extracts 1 and 2 were combined. The combined extract (116.5 g) contained 8.6 g of (2S)-2-hydroxy-3-phenylpropionic acid (yield 86%, optical purity 95.9% ee). The proton concentration (normality) in the reaction of this example was 1.7 mol/kg, the amount of the protonic acid was 3.0 equivalents (relative to L-phenylalanine), and the reaction temperature was 20° C.

Source