N-Formylmorpholine → 4-Bromo-2-(trifluoromethoxy)benzaldehyde

Temperature

-74 °C

Add 4-bromo-1-iodo-2-(trifluoromethoxy)benzene (22.04 g, 60 mmol) to a 1000 mL 3-neck flask equipped with a magnetic stir bar, thermocouple, addition funnel, and N2 inlet and replace the atmosphere in the flask with nitrogen. After adding anhydrous THF (300 mL), cool the mixture to −74° C. and treat dropwise with a solution of t-butyllithium (70 mL of 1.7 M solution, 120 mmol). Stir the resulting solution for 90 minutes and then treated dropwise with a solution of N-formyl morpholine (14.52 g, 126 mmol) in THF (15 mL). Stir the mixture an additional 15 minutes at −74° C. and then allow to warm to 0° C. over 1 hour. Quench the reaction by the adding 0.25 M citric acid (200 mL) and extract with ethyl acetate (1×300 mL). Wash the organic layer with saturated sodium chloride solution (1×200 mL), dry over anhydrous magnesium sulfate, filter through Celite®, and concentrate to an oil. Purify the crude product via silica gel chromatography eluting with hexanes to afford 8.24 g (51%) of the product as white crystals: 1H NMR (300 MHz, CDCl3) δ 10.32 (s, 1H), 7.85 (d, J=8.3 Hz, 1H), 7.63-7.53 (m, 2H).

1. customequipped with a magnetic stir bar
2. additionthermocouple, addition funnel, and N2 inlet
3. stirringStir the mixture an additional 15 minutes at −74° C.
4. temperatureto warm to 0° C. over 1 hour
5. customQuench
6. customthe reaction by the adding 0.25 M citric acid (200 mL)
7. extractionextract with ethyl acetate (1×300 mL)
8. washWash the organic layer with saturated sodium chloride solution (1×200 mL)
9. dry with materialdry over anhydrous magnesium sulfate
10. filtrationfilter through Celite®
11. concentrationconcentrate to an oil
12. customPurify the crude product via silica gel chromatography
13. washeluting with hexanes

ORD record

ord-66172e84a688496e9ca4e13f8508a90d

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08088776B2