2,3-Dihydroxybutanedioic Acid → Benzenepropanoic acid, a-(1-aminoethyl)-3-cyano-, methyl ester, [R-(R*,R*)]-

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Reaction Conditions

Reaction Steps

To a suspension of methyl β-aminobutyrate p-toluenesulfonic acid salt (4 g, 13.8 mmol) in THF cooled to −20 ° C. was added LiHMDS (28.4 mmol, 2.05 eq.) A THF solution of α-bromo m-tolunitrile (2.57 g, 13.1 mmol) was added. Upon completion the reaction was quenched with 5% NaHCO3 and concentrated. The residue was partitioned between water and methyl propi-onate. The water layer was extracted with another portion of methyl propionate. The combined organic layer was dried over MgSO4 and filtered. To the filtrate, tartaric acid (2.95 g, 19.66 mmol) was added and stirred overnight. The solid was filtered, washed with methyl propionate, and dried to yield the tartaric salt of methyl β-amino-α-(3-cyanophenylmethyl)butyrate (3.91 g, 74% yield). HPLC and NMR confirm formation of the desired product. 1H NMR for the tartrate salt: (500 MHz, DMSO) δ 7.71-7.51 (m, 4H), 4.32 (s, 2H), 3.53 (overlapping multiplet and a singlet, 4 H). HPLC indicated purity >99% and the diastereomer ratio to be 17:1 anti:syn (R,R:R,S). β-amino-α-(3-cyanophenylmethyl)butyrate is the anti diastereomer.

Provenance & Evidence