1-(diethoxyphosphorylmethyl)-2-fluorobenzene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The following phosphonate reagents were also prepared by the above-described method: diethyl 3-thienylmethylphosphonate, diethyl 2-furanylmethylphosphonate, diethyl 2-fluorobenzylphosphonate, and diethyl 3,4,5-trimethoxybenzylphos-phonate.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The following phosphonate reagents were also prepared by the above-described method: diethyl 3-thienylmethylphosphonate, diethyl 2-furanylmethylphosphonate, diethyl 2-fluorobenzylphosphonate, and diethyl 3,4,5-trimethoxybenzylphos-phonate.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The following phosphonate reagents were also prepared by the above-described method: diethyl 3-thienylmethylphosphonate. diethyl 2-furanylmethylphosphonate, diethyl 2-fluorobenzylphosphonate, and diethyl 3,4,5-trimethoxybenzylphos-phonate.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-5-fluoroisonicotinaldehyde (2 g, 9.80 mmol) and diethyl 2-fluorobenzylphosphonate (2.66 g, 10.78 mmol) in tetrahydrofuran (80 mL) at 0° C., was added potassium tert-butoxide(1M in tetrahydrofuran, 12.75 mL, 12.75 mmol) dropwise over a couple of minutes. When addition was complete, the reaction was allowed to stir at 0° C. for 45 min and quenched by addition of saturated ammonium chloride. The reaction was diluted with ether, washed with water (4×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (8%→15% EtOAc/Hex) gave 450 mg as an oil with solid crystallizing from the mixture. The material was triturated with hexanes (2×) to give a fine white powder. 1H NMR (CDCl3) δ: 8.26 (d, J=1.5 Hz, 1H), 7.69 (d, J=5.5 Hz, 1H), 7.64 (td, J=7.6, 1.5 Hz, 1H), 7.54 (d, J=16.8 Hz, 1H), 7.30-7.41 (m, 1H), 7.17-7.26 (m, 2H), 7.11-7.17 (m, 1H). 13C NMR (CDCl3) δ: 161.0, 156.7, 138.8, 136.6, 135.5, 131.0, 129.3, 127.9, 124.6, 123.7, 119.4, 116.3. 19F NMR (CDCl3) δ: −116.72 (br. s., 1F), −136.08 (br. s., 1F). When addition quenched by addition of saturated ammonium chloride The reaction was diluted with ether washed with water (4×) brine, dried over magnesium sulfate concentrated Column chromatography (8%→15% EtOAc/Hex) gave 450 mg as an oil with solid crystallizing from the mixture The material was triturated with hexanes (2×) to give a fine white powder

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-5-fluoroisonicotinaldehyde (2 g, 9.80 mmol) and diethyl 2-fluorobenzylphosphonate (2.66 g, 10.78 mmol) in tetrahydrofuran (80 mL) at 0° C., was added potassium tert-butoxide(1M in tetrahydrofuran, 12.75 mL, 12.75 mmol) dropwise over a couple of minutes. When addition was complete, the reaction was allowed to stir at 0° C. for 45 min and quenched by addition of saturated ammonium chloride. The reaction was diluted with ether, washed with water (4×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (8%→15% EtOAc/Hex) gave 450 mg as an oil with solid crystallizing from the mixture. The material was triturated with hexanes (2×) to give a fine white powder. 1H NMR (CDCl3) δ: 8.26 (d, J=1.5 Hz, 1H), 7.69 (d, J=5.5 Hz, 1H), 7.64 (td, J=7.6, 1.5 Hz, 1H), 7.54 (d, J=16.8 Hz, 1H), 7.30-7.41 (m, 1H), 7.17-7.26 (m, 2H), 7.11-7.17 (m, 1H). 13C NMR (CDCl3) δ: 161.0, 156.7, 138.8, 136.6, 135.5, 131.0, 129.3, 127.9, 124.6, 123.7, 119.4, 116.3. 19F NMR (CDCl3) δ: −116.72 (br. s., 1F), −136.08 (br. s., 1F). When addition quenched by addition of saturated ammonium chloride The reaction was diluted with ether washed with water (4×) brine, dried over magnesium sulfate concentrated Column chromatography (8%→15% EtOAc/Hex) gave 450 mg as an oil with solid crystallizing from the mixture The material was triturated with hexanes (2×) to give a fine white powder

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared according to the method used to prepare diethyl 3-fluorobenzylphosphonate starting with 1-(bromomethyl)-2-fluorobenzene. 1H NMR (CDCl3) δ: 7.36 (t, J=7.5 Hz, 1H), 7.19-7.25 (m, 1H), 7.07-7.13 (m, 1H), 7.04 (t, J=9.2 Hz, 1H), 3.99-4.08 (m, 4H), 3.15-3.24 (m, 2H), 1.25 (td, J=7.0, 0.9 Hz, 6H). Prepared

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The following phosphonate reagents were also prepared by the above-described method: diethyl 3-thienylmethylphosphonate, diethyl 2-furanylmethylphosphonate, diethyl 2-fluorobenzylphosphonate, and diethyl 3,4,5-trimethoxybenzylphos-phonate.