2-AMINO-4-FLUOROPYRIDINE

White powder

The 28 g 2 - amino -4 - chloro pyridine is added to the 100 ml of N, N - dimethyl formamide in, adding 46 g sodium fluoride, reaction 140 °C reaction 5 - 8 hours, cooling to 80 °C, pressure reducing and recovering the solvent, the residue is added in dichloromethane and saturated salt water distribution, organic phase solvent, ethanol recrystallization to obtain 2 - amino 4 - fluoro pyridine, white solid, 22 g, yield 90percent.Intermediate 50 (120 g, 565 mmol) was dissolved in DCM (1250 mL) and cooled with an ice bath. Trifluoroacetic acid (250 mL) was added dropwise. The resulting mixture was stirred overnight at ambient temperature. The mixture was concentrated andpartitioned between saturated aqueous sodium bicarbonate solution and EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried with sodium sulphate, filtered and concentrated, to afford the title compound (65.5 g) as a yellow solid. LCMS 113 [M+H], RT 0.17 minutes.INTERMEDIATE 124-Fluoropyridin-2-amineIntermediate 11 (120 g, 565 mmol) was dissolved in DCM (1250 mL) and cooledwith an ice bath. Trifluoroacetic acid (250 mL) was added dropwise. The resultingmixture was stirred overnight at ambient temperature. The mixture was concentrated and partitioned between saturated aqueous sodium bicarbonate solution and EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried with sodium sulphate, filtered and concentrated, to afford thetitle compound (65.5 g) as a yellow solid. Method B HPLC-MS m/z 113 [M+H], RT0.17 minutes.Immediately add 45percent HBF4 water to solid compound d obtained by rotary evaporation of the above solutionSolution (600mL, 10.8mo1), After stirring, the solid was completely dissolved and ethanol (200 mL) was added.Ice salt bath cooled to below -5°C, Isoamyl nitrite (150 mL, 1.12 mol) was added dropwise.Control temperature does not exceed 0 °C, And stir the reaction below 0°C for 3h.After the reaction was completed, tetrahydrofuran (200 mL) was added.Cool to below 0°C, Suction filtrationThe solid was washed twice with tetrahydrofuran (20 mL) and dried in a vacuum desiccator to obtain a solid compound e (213.25 g, 85.3percent) with a purity of 96percent.The diazonium fluoborate (250g, 1mo1) was put into a dry 1L triple reaction flask.Heat to 120°C, Solid decomposition, White smoke emerged from the reaction flask.Continue heating to exhaust white smoke.Solid decomposition is complete.Prepare a 40percent NaOH solution (300 mL)The solids on the condenser tube are washed into the reaction flask.Heat reflux, As the product is sublimated, The continuous condensation of solids on the condenserCollect the solids, Repeat the above operation, 2-amino-4-fluoropyridine (70 g, 62.5percent) was obtained, 98percent purity.

Molecular Weight:112.10
XLogP3:0.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:112.04367633
Monoisotopic Mass:112.04367633
Topological Polar Surface Area:38.9
Heavy Atom Count:8
Complexity:76.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes