Water → HCID 86679997, compound

Participants

Reaction Steps

To a solution of 5-azido-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ol (4.0 g, 14.2 mmol) in dry DCM (100 mL) cooled to 0° C. was added slowly triethylamine (4.0 mL, 28.5 mmol) followed by DMAP (175 mg, 1.42 mmol) and 4-methylbenzene-1-sulfonyl chloride (4.1 g, 21.4 mmol) portionwise. The reaction mixture was allowed to warm to room temperature and stirred for 18 hr. More 4-methylbenzene-1-sulfonyl chloride (1.4 g, 7.12 mmol) was added to the reaction mixture, which was stirred at room temperature for a further 24 hr. Water (40 mL) was added and the mixture was extracted with DCM (100 mL). The organic layer was separated, dried over MgSO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (30-70% EtOAc/isohexane) gave 5-azido-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl 4-methylbenzenesulfonate as a dark cream solid (2.81 g). This solid (2.3 g, 5.29 mmol) was treated with a solution of TBAF (1.0 M in THF, 21 mL, 21.1 mmol) and the reaction mixture was heated at 60° C. for 2 hr. After cooling to room temperature, water (30 mL) was added and the mixture was extracted with EtOAc (2×150 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (30-40% EtOAc/isohexane) gave 4-azido-5-fluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepane as a yellow viscous oil (804 mg, 20% over two steps) 1H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 5.06 (ddt, J=46.2, 8.1, 2.5 Hz, 1H), 4.00 (dd, J=20.8, 8.1 Hz, 1H), 3.79 (s, 3H), 3.43-3.34 (m, 2H), 3.26-3.11 (m, 2H), 2.43-2.30 (m, 1H), 2.30-2.18 (m, 1H), 2.12-1.92 (m, 2H).

Provenance & Evidence