4-Nitrophenol → HCID 178509009, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 5-fluoro-1-[cis-3-(hydroxymethyl)cyclobutyl]uracil (139 mg, 0.65 mmol) and methylpyrrolidine (530 mg, 6.2 mmol) in anhydrous CH3CN was treated dropwise with chlorotrimethylsilane (211 mg, 1.9 mmol). The mixture was aged for 1 h at ambient temperature, cooled to 0° C. and treated dropwise over 5 min. with trifluoroacetic anhydride (680 mg, 3.2 mmol). After 40 min. at 0° C. 4-nitrophenol was added to the mixture, and the mixture aged for an additional 2 h at 0° C. The mixture was poured into saturated sodium bicarbonate solution (20 mL) and extracted with CH2Cl2 (3×40 mL). Combined organic phases were dried over magnesium sulfate and then concentrated. The residue was dissolved in dioxane (10 mL) and 30% aqueous NH4OH (2.5 mL) and heated at 50° C. for 40 h in a sealed vessel. The mixture was cooled to ambient temperature and concentrated under vacuum. The resulting residue was purified by chromatography on silica gel with 10% CH3OH in CH2Cl2 with 1% NH4OH (v/v) to give 5-fluoro-1-[cis-3-(hydroxymethyl)-cyclobutyl]cytosine (53 mg, 38%) as a white solid and recovered starting material (50 mg). 1H NMR (DMSO-d6, 400 MHz): δ 1.89 (m, 2H), 2.09 (m, 1H), 2.24 (m, 2H), 3.39 (d, J=5.1 Hz, 2H), 4.56 (broad s, 1H, OH), 4.64 (m, 1H), 7.36 (broad s, 1H, NH2), 7.58 (broad s, 1H, NH2), 7.97 (d, J=7.2 Hz, 1H); MS (FAB): expected for C9H12FN3O2 (M+Li)+220.2. Found 220.19.

Provenance & Evidence