Reacción #364846

Ecuación de reacción

2-chloro-4-fluoro-5-iodo-anisole

hydrogen chloride

n-butyl lithium

trimethyl borate

→

4-chloro-2-fluoro-5-methoxyphenylboronic acid

Disolventes

diethyl ether

hexane

diethyl ether

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe temperature below −69° C.
2. 2
   workup.STIRRINGthe reaction mixture stirred 3 h
3. 3
   workup.STIRRINGthe resulting biphase system stirred 1 h
4. 4
   OtroThe separated aqueous phase was separated
5. 5
   Lavadowashed with an additional 30 ml of diethyl ether
6. 6
   LavadoCombined organic layers were washed with brine
7. 7
   Secadodried over magnesium sulfate
8. 8
   OtroEvaporating in vacuo
9. 9
   Otrogave a white solid which
10. 10
    Filtraciónfiltered
11. 11
    Otrodried

Procedimiento

To 2.0 g (7.0 mmol) of 2-chloro-4-fluoro-5-iodo-anisole (made from the compound of Example 11, Step A by methylation) stirring in 30 ml of diethyl ether at −78° C., 4.8 ml (7.7 mmol) of 1.6M n-butyl lithium was added dropwise (keeping the temperature below −69° C.). After stirring 0.5 h, 0.91 ml (8.0 mmol) of trimethyl borate in 15 ml of diethyl ether was added dropwise and the reaction mixture stirred 3 h before allowing to warm to room temperature. Slowly, 1N aqueous hydrogen chloride was added and the resulting biphase system stirred 1 h. The separated aqueous phase was separated and washed with an additional 30 ml of diethyl ether. Combined organic layers were washed with brine and dried over magnesium sulfate. Evaporating in vacuo gave a white solid which was suspended in hexane, filtered, and dried to afford 0.86 g of a technical sample of 4-chloro-2-fluoro-5-methoxyphenylboronic acid (m.p. 280-296° C.).

Fuente