(3R)-3-methyl-6-(oxiran-2-yl)-3,4-dihydro-1H-isochromen-1-one → (3R)-6-(1-Hydroxy-2-(9-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)ethyl)-3-methylisochroman-1-one

Participants

Reaction Steps

(3R)-6-(1-Hydroxy-2-(9-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)ethyl)-3-methylisochroman-1-one was prepared initially as a mixture of two diastereomers from 5-[(1R)-1-hydroxy-2-(3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)ethyl]-4-methyl-2-benzofuran-1(3H)-one [INTERMEDIATE 17] and (3R)-3-Methyl-6-(oxiran-2-yl)-3,4-dihydro-1H-isochromen-1-one [INTERMEDIATE 23, STEP B] in an analogous fashion to that described for the synthesis of EXAMPLE 1. The mixture of diastereomers was separated by preparative SFC-HPLC using a Chiralcel® OD column (30×250 mm) to afford the title single isomers.

Provenance & Evidence