Benzaldehyde → (S)-N-Benzylglutamic acid

HRID 2050933Notes

Reaction equation

HRID 2050933 reaction equation
O=C1N([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C@H](CC=O)CC1.[NH2:17][C@H:18]([C:24]([OH:26])=[O:25])[CH2:19][CH2:20][C:21]([OH:23])=[O:22].C(=O)C1C=CC=CC=1.[BH4-].[Na+]>>[C:8]1([CH2:7][NH:17][C@H:18]([C:24]([OH:26])=[O:25])[CH2:19][CH2:20][C:21]([OH:23])=[O:22])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 4

HCID 240BenzaldehydeHCID 33032L-Glutamic AcidHCID 4311764Sodium borohydrideHCID 10330963(S)-5-oxo-1-(phenylmethyl)-2-pyrrolidineacetaldehyde

Product 1

HCID 11107380(S)-N-Benzylglutamic acid

Procedure

The process set forth in Scheme I comprises the preparation of the intermediate, (S)-5-oxo-1-(phenylmethyl)-2-pyrrolidineacetaldehyde (10a). Thus, L-glutamic acid (3) can be reductively alkylated with benzaldehyde and sodium borohydride to yield the N-(1-phenylmethyl)-L-glutamic acid (4a). Acidification of the solution with hydrochloric acid to pH 3, followed by heating at reflux and then esterification of the crude product with methanol and sulfuric acid in toluene gives the (S)-5-oxo-1-(phenylmethyl)-2-pyrrolidinecarboxylic acid methyl ester (5). Reduction of (5) with sodium borohydride in methanol and t-butanol gives the hydroxymethyl compound characterized by formula (6). The optical purity of (S)-5-(hydroxymethyl)-1-(phenylmethyl)-2-pyrrolidinone (6), can be established by formation of the ester derived from (S)-(-)-α-methoxy-α-(trifluoromethyl)phenylacetic acid ((-)-MTPA) following the procedure of Mosher, et al. [J. Org. Chem. 1969, 34, 2543]. Conversion of (6) to the tosylate (7) was accomplished by treatment with p-toluenesulfonyl chloride and 4-dimethylaminopyridine. Treatment of the tosylate (7) with sodium iodide in acetone at reflux gives the iodide (8). Coupling of (8) with vinylmagnesium chloride, catalyzed by dilithium tetrachlorocuprate, leads to the propenyl compound (9), which can be ozonized in methanol with a methyl sulfide workup to yield the aldehyde, (S)-5-oxo-1-(phenylmethyl)-2-pyrrolidineacetaldehyde (10a). All of the steps described in Scheme I can be carried out using DL-glutamic acid or D-glutamic acid as the starting material, if it is desired to prepare enantiomeric or racemic (10a). ##STR19##

Sources & evidence

ORD record
ord-feca0936f0ab4171ac338215abc88b21
Source dataset
uspto-grants-1991_05
Patent number
US05015653

Reaction notes

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