Diethyl chlorophosphate → Diethyl (4-fluoronaphthalen-1-yl)phosphonate

Temperature

-78 °C

A solution of 1-bromo-4-fluoronaphthalene (500 mg, 2.22 mmol) in tetrahydrofuran (5 mL) was added dropwise to stirred solution of t-BuLi (1.4 M in pentane, 3.17 mL, 4.44 mmol) in tetrahydrofuran (5 mL) at −78° C. The reaction mixture was stirred for 1 hour at −78° C., after which diethyl chlorophosphate (0.96 mL, 6.66 mmol) was added dropwise. The reaction mixture was left to warm to rt and concentrated. The residue was suspended in 2 M NaOH (50 mL) and extracted with dichloromethane (2×50 mL). The combined organic phases were dried over sodium sulfate, filtered and evaporated to give crude (4-fluoronaphthalen-1-yl)phosphonic acid diethyl ester (139MBT60-8C, 512 mg, 60% pure by NMR) as a yellow oil. 139MBT60-8C (200 mg, 0.425 mmol) was dissolved in pyrrolidine (0.5 mL) and stirred 2 hours at rt. The reaction mixture was concentrated and re-dissolved in dichloromethane (20 mL). The organic phase was washed with 2 M NaOH (20 mL) and dried over sodium sulfate, filtered and evaporated. The residue was purified by preparative TLC (0-5% methanol in dichloromethane) to give the title compound (89 mg, 30%) as a white solid.

1. waitThe reaction mixture was left
2. temperatureto warm to rt
3. concentrationconcentrated
4. extractionextracted with dichloromethane (2×50 mL)
5. dry with materialThe combined organic phases were dried over sodium sulfate
6. filtrationfiltered
7. customevaporated

ORD record

ord-69a7eec961274cee9a99f76fba6b06ab

Source dataset

uspto-grants-2007_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07268232B2