13 April 2013

Synthesis: (S)-2-amino-3-(3-phenylacetylimidazol-4-yl)propanoic acid

Synthesis of 2-Amino-3-(3-phenylacetylimidazol-4-yl)propanoic acid.
Laminar flow chemical hood
Magnetic stirrer/hot plate
L-Histidine (Sigma ) 
Phenylacetyl chloride (Aldrich )
Whatman #2 filter paper
400ml beaker
1000ml Ehrlenmeyer filter flask
Buchner funnel
Evaporation plates (2)

47.32g His
~48 ml PAC
10:00am - 11:30am
Rx in 400ml beaker w/stir bar
Temp. = 50*-65*C
7.5ml (500ul aliquots)1N NaOH added to Rx at 11:30am
50ml H2O added at 11:35
3.25ml 1N NaOH added at 11:45am
Temp. = 55*C at 11:55
Stop Rx at 12:00
Vacuum filter (#2 Whatman paper in Buchner funnel) into 1000ml Ehrlenmeyer filter flask
Pour eluant into evaporation plates (2)
Rinse flask w/ H2O- pour into evaporation plates.
Evaporate to dryness in laminar flow hood.
HPLC Q.C. check:
C-18 column
Mobile phase: 80 parts H2O, 20 parts CH3OH, 1 part CH3COOH
flow rate: 1ml/min
qualitative analysis performed on three (3) aliquots:
1.) Histidine control
2.) Rx beaker - after 1 hr Rx
3.) Filtered eluant (product)
Histidine control graph shows no product peaks or phenylacetic acid peak.
Rx aliquot has unreacted histidine peak, 2-amino-3-(3-phenylacetylimidazol-4-yl)propanoic acid peak, 2-amino-3-(1-phenylacetylimidazol-4-yl)propanoic acid peak, phenylacetyl linkage on primary amine of histidine (phenylacetyl - histidine) peak, phenylacetic acid peak.
Filtered eluant (product) aliquot has only product peak - 2-amino-3-(3-phenylacetylimidazol-4-yl)propanoic acid + very small (<5%) isomer peak (2-amino-3-(1-phenylacetylimidazol-4-yl)propanoic acid)

Thank you.


Dennis Wright