N,N-Dimethylaniline → 3-Bromo-5-fluorophenol

To a solution of 1-bromo-3-fluoro-5-benzyloxybenzene (110.0 g, 0.39 mol; see step (i) above) and N,N-dimethylaniline (474.0 g, 3.92 mol) in anhydrous CH2Cl2 (1.0 L) at 0° C. was added aluminium chloride (156.0 g, 1.17 mol). After 10 min, the ice bath was removed and the stirring was continued for 2 h. The reaction was quenched by the cautious addition of 3N HCl (600 mL). The layers were separated, and the aqueous layer was extracted with CH2Cl2 (2× 150 mL). The combined organic extracts were washed with 2N HCl (250 mL) and H2O (3× 250 mL). To the organic layer was added 15% KOH (500 mL), and the layers were separated. The organic layer was further extracted with 2 N KOH (2× 70 mL). The combined aqueous layers were washed with CH2Cl2 (3× 100 mL) and then acidified with 4N HCl. The aqueous layer was extracted with Et2O (3× 125 mL) then, the combined Et2O extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford the sub-title compound (69.0 g, 92%) as a brown oil that was used without further purification.

1. customthe ice bath was removed
2. waitthe stirring was continued for 2 h
3. customThe reaction was quenched by the cautious addition of 3N HCl (600 mL)
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with CH2Cl2 (2× 150 mL)
6. washThe combined organic extracts were washed with 2N HCl (250 mL) and H2O (3× 250 mL)
7. additionTo the organic layer was added 15% KOH (500 mL)
8. customthe layers were separated
9. extractionThe organic layer was further extracted with 2 N KOH (2× 70 mL)
10. washThe combined aqueous layers were washed with CH2Cl2 (3× 100 mL)
11. extractionThe aqueous layer was extracted with Et2O (3× 125 mL)
12. dry with materialthe combined Et2O extracts were dried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD record

ord-ce32bdd71d1c48838bc27abaa787f6c7

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07645751B2