반응 #1003509

반응 방정식

1-bromo-4-fluoronaphthalene

t-BuLi

diethyl chlorophosphate

→

(4-fluoronaphthalen-1-yl)phosphonic acid diethyl ester

수율 81.7%

용매

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.WAITThe reaction mixture was left
2. 2
   온도to warm to rt
3. 3
   농축concentrated
4. 4
   추출extracted with dichloromethane (2×50 mL)
5. 5
   건조The combined organic phases were dried over sodium sulfate
6. 6
   여과filtered
7. 7
   기타evaporated

실험 절차

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.

출처