Phosphorodichloridic acid, phenyl ester → 4-Bromo-2-methoxybenzonitrile

A solution of 4-bromo-2-methoxybenzamide (508 mg, 2.21 mmol) in anhydrous DCM (10 mL) was cooled to 0° C. and then treated with 1,8-diazabicyclo(5.4.0)undec-7-ene (0.991 mL, 6.62 mmol). The mixture was stirred at 0° C. for 15 min, and then treated with phenyl dichlorophosphate (0.660 mL, 4.42 mmol) over 2 min. The reaction was stirred at 0° C. for 10 min, and then warmed to RT where it stirred for 1 h. After this time, the mixture was partitioned between DCM (10 mL) and saturated NH4Cl (20 mL). The aqueous phase was extracted with DCM. The combined extracts were dried (MgSO4) and concentrated to give the crude product, which was purified by flash chromatography (12 g SiO2 column; 0-30% EtOAc/Hex gradient) to give 4-bromo-2-methoxybenzonitrile (250 mg, 1.18 mmol, 53% yield) as a white solid. 1H-NMR (400 MHz, CDCl3) δ ppm 7.40 (1H, s), 7.16 (1H, s), 7.12 (1H, s), 3.91 (3H, s).

1. stirringThe reaction was stirred at 0° C. for 10 min
2. temperaturewarmed to RT where it
3. stirringstirred for 1 h
4. customAfter this time, the mixture was partitioned between DCM (10 mL) and saturated NH4Cl (20 mL)
5. extractionThe aqueous phase was extracted with DCM
6. dry with materialThe combined extracts were dried (MgSO4)
7. concentrationconcentrated
8. customto give the crude product, which
9. customwas purified by flash chromatography (12 g SiO2 column; 0-30% EtOAc/Hex gradient)

ORD-Eintrag

ord-844ed5792e1343419f54752457a5b244

Quelldatensatz

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08354432B2