Hydrochloric Acid → (4-Chloro-2-fluoro-5-methoxyphenyl)boronic acid

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.).

1. customthe temperature below −69° C.
2. stirringthe reaction mixture stirred 3 h
3. stirringthe resulting biphase system stirred 1 h
4. customThe separated aqueous phase was separated
5. washwashed with an additional 30 ml of diethyl ether
6. washCombined organic layers were washed with brine
7. dry with materialdried over magnesium sulfate
8. customEvaporating in vacuo
9. customgave a white solid which
10. filtrationfiltered
11. customdried

ORD record

ord-1a8bb95a32194dfc97b641b7dea6ae0f

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06358885B1