Acetic Acid → 3-(5-Acetoxy-6-bromohexyl)-1-methylthymine

Participants

Reaction Steps

A mixture of 3-(5,6-dihydroxyhexyl)-1-methylthymine (1.65 g, 6.4 mmol) and a 30% solution of hydrogen bromide in acetic acid (3.8 mL, 19.3 mmol) in water (5 mL) and acetone (10 mL) was stirred for 1.5 hours. The mixture was then added to a flask containing sodium bicarbonate (6.7 g), water (40 mL) and dichloromethane (50 mL). After 15 minutes of vigorous stirring, the layers were separated and the aqueous layer washed with dichloromethane (2×50 mL). The combined organic layers were dried over sodium sulfate. The solvent was evaporated under vacuum to yield 2.30 g (100%) of 3-(5-acetoxy-6-bromohexyl)-1-methylthymine as a yellow oil. The bromoacetate was used in the next step without further purification. A solution of 3-(5-acetoxy-6-bromohexyl)-1-methylthymine (2.30 g, 6.4 mmol) in methanol (10 mL) was treated with a 1 M methanol solution of sodium methoxide (7 mL). After stirring for 15 minutes, the solution was poured into water (60 mL) and extracted with 20% ethanol/dichloromethane (2×70 mL). The combined organic layers were dried over sodium sulfate and the solvent evaporated under vacuum to yield 1.30 g (85%) 3-(5,6-oxidohexyl)-1-methylthymine as a white solid.

Provenance & Evidence