4-Fluoro-2-methoxypyridine

[311] To a 0 C solution of 3-nitro-1H-pyrazole (1.0 g, 8.84 mmol) in DMF (8.0 mL) was added NaH (450 mg of 60 %w/w, 11.25 mmol). After 20 minutes, the mixture was warmed to room temperature and stirred a further 60 min. 4-fluoro-2-methoxy-pyridine (1.29 g, 10.15 mmol) was added, and the resultant reaction mixture was stirred for 16 h at room temperature followed by 80 C for 6 h. The reaction mixture was poured over ice, and a colorless precipitate formed. The product was collected by vacuum filtration, and the solids air-dried to provide 2-methoxy-4-(3-nitro-1H-pyrazol-1-yl)pyridine (692 mg, 35% yield). 1H NMR (300 MHz, DMSO-d6) delta 8.97 (t, J = 2.4 Hz, 1H), 8.36 (dd, J = 5.7, 1.9 Hz, 1H), 7.59 (dt, J = 5.7, 1.9 Hz, 1H), 7.41 (dt, J = 6.6, 2.0 Hz, 2H), 3.94 (d, J = 1.9 Hz, 3H) ppm. ESI-MS m/z calc. 220.06, found 221.08 (M+1).In analogy to the preparation of the intermediate 10-1 (step 1) from tert-butyl N- [(lR, 5S, 8S)-3-azabicyclo[3.2.1]octan-8-yl]carbamate (2.00 g, 8.84 mmol) and 4-fluoro-2- methoxypyridine (1.12 g, 8.84 mmol) in a sealed tube at 140 C using NMP as solvent in the presence of DIPEA (2.28 g, 3.09 mL, 17.70 mmol), tert-butyl N-[(lR, 5S, 8S)-3-(2-methoxy-4- pyridyl)-3-azabicyclo[3.2.1]octan-8-yl]carbamate (1.42 g, 48%) was obtained as a white solid. MS (ES+) m/z: 334.3 [(M+H)+].In analogy to the preparation of the intermediate 8-1 (step 1) from tert-butyl N- [(lR, 5S, 8S)-3-azabicyclo[3.2.1]octan-8-yl]carbamate (2.00 g, 8.84 mmol) and 4-fluoro-2- methoxypyridine (1.12 g, 8.84 mmol) in a sealed tube at 140 C using NMP as solvent in the presence of DIPEA (2.28 g, 3.09 mL, 17.70 mmol), tert-butyl N-[(lR, 5S, 8S)-3-(2-methoxy-4- pyridyl)-3-azabicyclo[3.2.1]octan-8-yl]carbamate (1.42 g, 48%) was obtained as a white solid. MS (ES+) m/z: 334.3 [(M+H)+].

Molecular Weight:127.12
XLogP3:1.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:127.043341977
Monoisotopic Mass:127.043341977
Topological Polar Surface Area:22.1
Heavy Atom Count:9
Complexity:89.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes