Boron Trichloride → 5-Amino-2-fluorophenol

Temperature

-75 °C

A solution of 50 g (0.354 mol) of 4-fluoro-3-methoxy-aniline dissolved in methylene chloride (1800 ml) was treated under argon with 163.2 g (0.44 mol) of tetrabutyl-ammonium iodide, cooled to −75° C. and the treated over a period of 25 minutes with 860 ml of 1 M BCl3 in methylene chloride while keeping the reaction solution between −75° C. and −64° C. The solution was stirred for 15 minutes the cooling bath was removed and stirring was continued for 24 h under argon. The reaction solution was poured into ice water (6 l) with stirring, the layers were separated, the water layer twice extracted with methylene chloride (each 1.5 l). The combined organic layers were washed twice with water (each 2 l) and discarded. The combined aqueous layers were made basic with solid NaHCO3, saturated with NaCl, extracted 3 times with 2.5 l of ether and twice with 1.5 l of AcOEt. The combined organic layers were tried over magnesium sulphate and concentrated in vacuo to give 43.9 g (87.8%) of 4-fluoro-3-hydroxy-aniline as light brown crystalline solid. Melting point: 156-157° C.

1. customthe reaction solution between −75° C. and −64° C
2. customwas removed
3. stirringstirring
4. waitwas continued for 24 h under argon
5. additionThe reaction solution was poured into ice water (6 l)
6. stirringwith stirring
7. customthe layers were separated
8. extractionthe water layer twice extracted with methylene chloride (each 1.5 l)
9. washThe combined organic layers were washed twice with water (each 2 l) and
10. extractionextracted 3 times with 2.5 l of ether
11. concentrationconcentrated in vacuo

ORD record

ord-205b89be5c314e33b322bc1ba2ad1c60

Source dataset

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06818767B2