Hydrochloric Acid → 4-(4-Hydroxybenzoyl)-L-phenylalanine

HRID 1603289Notes

Reaction equation

HRID 1603289 reaction equation
Cl[CH2:2][C:3]1[CH:17]=[CH:16][C:6]([C:7]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[O:8])=[CH:5][CH:4]=1.C(CC([NH:23][CH:24](C#N)[C:25]([O-:27])=[O:26])=O)C.Cl>>[OH:15][C:12]1[CH:13]=[CH:14][C:9]([C:7]([C:6]2[CH:16]=[CH:17][C:3]([CH2:2][C@@H:24]([C:25]([OH:27])=[O:26])[NH2:23])=[CH:4][CH:5]=2)=[O:8])=[CH:10][CH:11]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 19609276HCID 19609276, compoundHCID 77174707HCID 77174707, compound

Product 1

HCID 540726534-(4-Hydroxybenzoyl)-L-phenylalanine

Procedure

FIG. 1 is a schematic showing the synthesis of HBPA. 4-(Chloromethyl)benzoyl chloride (II) is made by refluxing 4-(chloromethyl)benzoic acid with oxalyl chloride in benzene. Mixing this compound with pyridine with gentle heating using a steam bath followed by ice quench gave 4-chloro-methylbenzoic anhydride (III). 4-Chloromethylbenzoic anhydride (III) is reacted with phenol in polyphosphoric acid to give the 4-chloromethylbenzoyl ester of 4-chloromethyl-4'-hydroxybenzophenone (IV). Reacting IV with ethylacetamidocyanoacetate and subsequent hydrolysis with concentrated HCl gives racemic p-(4-hydroxybenzoyl)phenylalanine (HBPA, VI). D,L-HBPA is derivatized using standard Fmoc chemistry for incorporation into the peptide (e.g., at position 8 of substance P) by solid-phase synthesis. Radioiodination of L-HBPA8 -SP is accomplished using Chloramine-T. See "Experimental Procedures" for details. HBPA can also be prepared by procedures disclosed in Horner and Medem., Chem. Ber., 85:520 (1952), the teachings of which are incorporated herein by reference.

Sources & evidence

ORD record
ord-35a2fefe9ded4300b5c1e66a270cbc25
Source dataset
uspto-grants-1999_11
Patent number
US05986136

Reaction notes

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