L-Phenylalanine, methyl ester → 33605-76-4

HRID 980522Notes

Reaction equation

HRID 980522 reaction equation
[CH:1]([NH:3][C@@H:4]1[C:9](=[O:10])[O:8][C:6](=[O:7])[CH2:5]1)=[O:2].[CH3:11][O:12][C:13](=[O:23])[C@H:14]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[NH2:15]>C(OCC)(=O)C>[CH3:11][O:12][C:13](=[O:23])[C@H:14]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[NH:15][C:9](=[O:10])[C@H:4]([CH2:5][C:6](=[O:7])[OH:8])[NH:3][CH:1]=[O:2]

Participants

4

Reactant 2

HCID 736234L-Phenylalanine, methyl esterHCID 11298025N-[(3S)-Tetrahydro-2,5-dioxo-3-furanyl]formamide

Product 1

HCID 1026805633605-76-4Yield 87%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

The resin used carries sulphonic acid groups on a polystyrene matrix and has an exchange capacity of 5 meq. per gram of dry resin. Consequently the ratio of the acid equivalents of the resin acid groups to the moles of N-formyl-L-aspartic anhydride is 0.1. The mass is agitated in the flask to obtain a suspension. The solution of L-phenylalanine methyl ester in ethyl acetate is added to this agitated suspension by means of the dropping funnel over a time of about 8 minutes, while maintaining the temperature of the mass at about 25° C. At the end of this time a solution is obtained from which the cation exchange resin is separated by filtration. The solution is then cooled to 0° C. and a crystalline precipitate is obtained constituted by a mixture of the α and β isomers of N-formyl-L-aspartyl-L-phenylalanine methyl ester (14.1 g, yield 87%). This precipitate is subjected to HPLC analysis in order to check the ratio of the α to the β by comparison with known samples. The HPLC determinations are carried out using a Perkin-Elmer chromatograph, series 3, with a 7 micron RP8 column, 250×4 mm; eluent used: continuous gradient between solvents: (A) 65 parts of monobasic potassium phosphate 0.07 molar at pH 4+35 parts of methanol; and (B) 65 parts of water +35 parts of methanol; flow rate 1 ml per minute.

Workup

  1. customto obtain a suspension
  2. customAt the end of this time a solution is obtained from which the cation exchange resin
  3. customis separated by filtration
  4. temperatureThe solution is then cooled to 0° C.
  5. customa crystalline precipitate is obtained

Sources & evidence

ORD record
ord-d017fcd1461549b7b69104f6c50571b0
Source dataset
uspto-grants-1987_01
Patent number
US04638081

Reaction notes

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