Patent ID: 7632948
Filing Date: 2009-12-15
Classification: C07D,C12P

Abstract:
1. A method of preparing the chiral (±) isomers of indole-2,3-dione-3-oxime compounds, which method comprises the sequential steps of: (i) reacting an 8-amino-1,2,3,4-tetrahydro-isoquinoline with chloral hydrate and hydroxylamine hydrochloride to give an N-(1,2,3,4-tetrahydro-isoquinolin-8-yl)-2-hydroxyimino-acetamide; (ii) adding sulphuric acid to the N-(1,2,3,4-tetrahydro-isoquinolin-8-yl)-2-hydroxyimino-acetamide obtained in step (i) to provide a 2,3-dioxo-2,3,6,7,8,9-hexahydro-1H-pyrrolo[3,2-h]isoquinoline; and (iii) reacting the 2,3-dioxo-2,3,6,7,8,9-hexahydro-1H-pyrrolo[3,2-h]isoquinoline obtained in step (ii) with chiral (enantiopure (R) or (S)) α-N,N-diBoc-aminoxy-γ-butyrolactone to obtain the desired chiral end product, i.e. enantiopure (R)- or (S)-2-[2-oxo-1,2,6,7,8,9-hexahydro-pyrrolo[3,2-h]isoquinolin-3-ylideneaminooxy]-4-hydroxy-butyric acid.