Triphenylphosphine → (3S,8S)-3-(3-cyclopentylmethoxy-phenyl)-8-{(S)-2-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

(3S,8S)-8-{(S)-2-[4-(2,3-Dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethyl-carbamoyl}-3-(3-hydroxy-phenyl)-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester (25 mg), cyclopentyl methanol (11 mg), triphenyl phosphine (38 mg) were taken in 1 mL of anhydrous DCM and cooled to 0° C. Diisobutyl azodicarboxylate (22 mg) was added and reaction was warned to room temperature and stirred for 4 hours. After the completion of the reaction, the reaction mixture was loaded onto a silica gel column (1:1 EtOAc:hexanes to 4% MeOH in 1:1 EtOAc:hexanes) to give (3S,8S)-3-(3-cyclopentylmethoxy-phenyl)-8-{(S)-2-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester (24 mg). This was taken up in 2 mL anhydrous DCM and cooled 0° C., HCl (0.5 mL, 4N in dioxane) was added and stirred at room temperature for 1 hour. All volatiles are evaporated and residue was precipitated from DCM/hexanes to get (S)-2-{[(3S,8S)-3-(3-cyclopentylmethoxy-phenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester dihydrochloride (22 mg).

Provenance & Evidence