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

Objective:

 

Synthesis of 2-Amino-3-(3-phenylacetylimidazol-4-yl)propanoic acid.

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Materials:

Laminar flow chemical hood
Magnetic stirrer/hot plate
L-Histidine (Sigma ) 

Phenylacetyl chloride (Aldrich )
1N NaOH
Whatman #2 filter paper
dH20
Thermometer
400ml beaker
1000ml Ehrlenmeyer filter flask
Buchner funnel
Evaporation plates (2)

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Procedure:

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.

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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)
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Thank you.

Regards,

Dennis Wright
drwright442000@yahoo.com