Hydrochloric Acid → (S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester 8-methyl ester

Participants

Reaction Steps

To a solution of (S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-3-hydroxy-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester 8-methyl ester (122 mg) in DCM (10 mL) were added TFA (1 mL) and triethylsilane (3 eq) at −10° C. and the reaction mixture were stirred and allowed to warm up to room temperature within 3 h. Then the reaction mixture was concentrated in vacuo. To this residue di-tert-butyl dicarbonate (2 eq) and sodium bicarbonate (3.0 eq) were added in the presence of ethyl acetate (25 mL) and stirred at r.t. for 4 h. After t-boc protection was complete the reaction mixture was then slowly acidified with dilute HCl (25 mL, 1.0 M solution), extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with 1 N HCl (25 mL), water (25 mL) and brine (25 mL) dried over sodium sulfate, filtered, and concentrated to provide a yellow solid. The residue was then purified by silica gel chromatography (10/90 to 30/70 ethyl acetate/hexanes in 10% increments) to obtain a white solid of (S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester 8-methyl ester (73 mg).

Provenance & Evidence