1-(diethoxyphosphorylmethyl)-3,5-difluorobenzene

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

Procedure: Diethyl 3,5-difluorobenzylphosphonate (3.00 g, 11.4 mmol) was dissolved in dry dichloromethane (25 mL). Bromotrimethylsilane (4.9 mL, 37 mmol) was added via syringe. The reaction was capped with a greased glass stopper and allowed to stir for 6 hours. The volatiles were removed under reduced pressure to yield a yellow oil. This was dissolved in 8:1 methanol:water (25 mL) and allowed to stir overnight. After removing the solvents, recrystallization in acetonitrile yielded a white crystalline solid (1.98 g, 91% yield). 1H NMR (400.14 MHz, DMSO) δ 7.05 (dt, J=9.49, 2.09 Hz), 6.95 (d, J=8.54 Hz, 2H), 3.02 (d, J=21.57 Hz, 2H). 31P {1H} NMR (161.97 MHz, DMSO): δ 20.63. Analysis calculated (found) %: C, 40.40 (40.67), H, 3.39 (3.39). The reaction was capped with a greased glass stopper The volatiles were removed under reduced pressure to yield a yellow oil to stir overnight After removing the solvents, recrystallization in acetonitrile

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,5-difluorobenzyl bromide (3.0 mL, 23.2 mmol) was combined with triethylphosphite (9.1 mL, 53.3 mmol) and the mixture heated and stirred at 135° C. overnight. The mixture was put under hi-vacuum and heated to 70° C. for 12 hours. The final product was a clear oil (5.78 g, 94% yield). 1H NMR (400.14 MHz, CDCl3) δ 6.83 (m, 2H), 6.71 (dt, J=9.00, 2.28 Hz), 4.06 (m, 4H), 3.12 (d, J=21.94 Hz, 2H), 1.28 (t, J=7.09 Hz, 6H). 31P{1H} NMR (161.97 MHz, CDCl3): δ 25.22. the mixture heated heated to 70° C. for 12 hours

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

Procedure: Diethyl 3,5-difluorobenzylphosphonate (3.00 g, 11.4 mmol) was dissolved in dry dichloromethane (25 mL). Bromotrimethylsilane (4.9 mL, 37 mmol) was added via syringe. The reaction was capped with a greased glass stopper and allowed to stir for 6 hours. The volatiles were removed under reduced pressure to yield a yellow oil. This was dissolved in 8:1 methanol:water (25 mL) and allowed to stir overnight. After removing the solvents, recrystallization in acetonitrile yielded a white crystalline solid (1.98 g, 91% yield). 1H NMR (400.14 MHz, DMSO) δ 7.05 (dt, J=9.49, 2.09 Hz), 6.95 (d, J=8.54 Hz, 2H), 3.02 (d, J=21.57 Hz, 2H). 31P {1H} NMR (161.97 MHz, DMSO): δ 20.63. Analysis calculated (found) %: C 40.40(40.67), H 3.39 (3.39). The reaction was capped with a greased glass stopper The volatiles were removed under reduced pressure to yield a yellow oil to stir overnight After removing the solvents, recrystallization in acetonitrile

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,5-difluorobenzyl bromide (3.0 mL, 23.2 mmol) was combined with triethylphosphite (9.1 mL, 53.3 mmol) and the mixture heated and stirred at 135° C. overnight. The mixture was put under hi-vacuum and heated to 70° C. for 12 hours. The final product was a clear oil (5.78 g, 94% yield). 1H NMR (400.14 MHz, CDCl3) δ 6.83 (m, 2H), 6.71 (dt, J=9.00, 2.28 Hz), 4.06 (m, 4H), 3.12 (d, J=21.94 Hz, 2H), 1.28 (t, J=7.09 Hz, 6H). 31P {1H} NMR (161.97 MHz, CDCl3): δ 25.22. the mixture heated heated to 70° C. for 12 hours