Tetrahydrofuran → Ethyl acetate methanol ammonium hydroxide

Participants

Reaction Conditions

Reaction Steps

To 2-[4-(2-amino-2-oxoethoxy)phenyl]-6-benzyloxy-3-[3-methoxy-4-[(1-pyrrolidinyl)methyl]benzyl]benzo[b]thiophene (93 mg, 0.15 mmol) in THF (5 mL) was added lithium aluminum hydride (57 mg) at ambient temperature and the mixture was stirred under argon at 65° C. for 24 h. The reaction was quenched with water (1 mL) and sodium hydroxide solution (1.0 M, 1 mL) while stirring continued for 30 min. The mixture was then diluted with brine (50 mL) and extracted with dichloromethane (30 mL×3). The combined organic layers were dried with sodium sulfate and concentrated in vacuo. The crude reduction product was dissolved in THF (5 mL) and treated with a 25% aqueous solution of ammonium formate (2 mL) and palladium on carbon (10%, 100 mg) at ambient temperature under argon for 6 h before filtration through diatomaceous earth followed by rinsing with dichloromethane and methanol. The filtrate was extracted with dichloromethane (30 mL×3) which was washed with water (50 mL). The combined organic layers were dried with sodium sulfate and concentrated under reduced pressure. Chromatography with NH4OH:MeOH:EtOAc (3:7:90) afforded the product as a white solid (24 mg, 31%).

Provenance & Evidence