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TCI Practical Example: Fluorination Using F-TEDA-BF₄

We are proud to present the difluorination of the 1,3-dicarbonyl compound using F-TEDA-BF₄.

Used Chemicals

• Acetoacetanilide [A0046]
• N-Fluoro-N'-(chloromethyl)triethylenediamine Bis(tetrafluoroborate) (= F-TEDA-BF₄) [F0358]
• Acetonitrile
• Water

Procedure

To a solution of acetoacetanilide (194 mg, 1.1 mmol) in acetonitrile and water (1:1, 4 mL) was added F-TEDA-BF₄ (778 mg, 2.2 mmol). The reaction mixture was stirred at r.t. for 24 hours. Then solvent was removed under reduced pressure and the residue was purified by column chromatography (ethyl acetate:hexane = 0:1 - 1:9 on silica gel) to give 2,2-difluoro-3-oxo-N-phenylbutanamide as a light yellow liquid (214 mg, yield 92%).

Experimenter's Comments

The reaction mixture was monitored by LC.

Analytical Data

2,2-Difluoro-3-oxo-N-phenylbutanamide

¹H NMR (270 MHz, CDCl₃); δ 7.97 (brs, 1H), 7.57-7.53 (m, 2H), 7.38 (t, 2H, J = 8.1 Hz), 7.25-7.18 (m, 1H), 6.60 (t, 1H, J = 73 Hz), 2.52 (t, 3H, J = 1.6 Hz).

Lead Reference

• Chemoselective Mono- and Difluorination of 1,3-Dicarbonyl Compounds
• L. Tang, Z. Yang, J. Jiao, Y. Cui, G. Zou, Q. Zhou, Y. Zhou, W. Rao, X. Ma, J. Org. Chem. 2019, 84, 10449.