2-Bromo-4-fluoropyridine synthesis

Yield:-

Reaction Conditions:

Stage #1:2-bromo-4-aminopyridine with tetrafluoroboric acid;sodium nitrite in water at 0 - 20; for 12.0833 h;
Stage #2: with sodium hydrogencarbonate in water

Steps:

5.1
Example 5N-(4-{[l-(4-fluoropyridin-2-yl)-lH-indol-5-yl]oxy}pyrimidin-2-yl)benzene-l,3-diamine (Compound 76)For the preparation of Compound 77, 2-bromo-4-fluoropyridine was prepared utilizing a modified procedure described in the reference below, and used in the indole arylation reaction. Thibault, C; L'ηeureux, A.; Bhide, R. S.; Ruel, R. Org. Lett. 2003, 5, 5023-5025.Step 1: 2-bromo-4-fluoropyridine.To a stirred suspension of 2-bromopyridin-4-amine (0.50 g, 2.9 mMol) in 50% aqueous HBF₄ (6.0 mL) was added a solution of sodium nitrite (0.24 g, 3.5 mMol) in water (3.0 mL) over 5 minutes at 0 ⁰C. The resulting mixture was allowed to warm to ambient, and was stirred for 12 hours. Solid NaHCO₃ was added slowly, until CO₂ evolution ceased, and the resulting aqueous solution was extracted with EtOAc (2 x 30 mL). The combined organic extracts were washed with saturated NaHCO₃ (1 x 30 mL), and brine (1 x 30 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to afford the title compound.

References:

MERCK & CO., INC. WO2007/35309, 2007, A1 Location in patent:Page/Page column 63

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