ChemicalBook CAS DataBase List 4-Fluoro-2-methylphenylboronic acid

4-Fluoro-2-methylphenylboronic acid synthesis

4synthesis methods

Product Name:4-Fluoro-2-methylphenylboronic acid
CAS Number:139911-29-8
Molecular formula:C7H8BFO2
Molecular Weight:153.95

5419-55-6

452-63-1

139911-29-8

The general procedure for the synthesis of 4-fluoro-2-methylphenylboronic acid from triisopropyl borate and 2-bromo-5-fluorotoluene was carried out as follows: 2-bromo-5-fluorotoluene (250 g) was dissolved in a solvent mixture of tetrahydrofuran (250 ml) and n-hexane (250 ml) under dry conditions, and cooled to -78 °C. At this temperature, n-butyllithium (991.5 ml) was slowly added dropwise and the reaction temperature was maintained in an ice bath. After the dropwise addition, the reaction mixture was stirred for 1 hour. Subsequently, triisopropyl borate (373.11 g) was added dropwise and stirring was continued at -78°C for 1 hour. After completion of the reaction, the reaction mixture was diluted with aqueous sodium hydroxide solution and then washed with n-heptane. The pH of the aqueous layer was adjusted to 2-3 with hydrochloric acid followed by extraction with ethyl acetate. The organic layers were combined and concentrated under vacuum. The concentrated product was dissolved in ethyl acetate at about 40 °C and n-heptane was added to promote crystallization, resulting in 4-fluoro-2-methylphenylboronic acid. The yield was 61.5% and the HPLC purity was 99.00%.

5419-55-6
396 suppliers
$12.00/5g

452-63-1 Synthesis

452-63-1
350 suppliers
$11.00/25g

139911-29-8
247 suppliers
$6.00/1g

Yield: 61.5%

Reaction Conditions:

Stage #1:2-Bromo-5-fluorotoluene with n-butyllithium in tetrahydrofuran;hexane at -78; for 1 h;
Stage #2:Triisopropyl borate in tetrahydrofuran;hexane for 1 h;

Steps:

1 Example 1: synthesis of 2-methyl-4-fluorophenylboronic acid
In a solution of 2-bromo-5-fluorotoluene (250 g) in tetrahydrofuran (250 ml) and n- hexane (250 ml) was added n-butyl lithium (991.5 ml) drop wise at -78°C in a dry-ice bath. The solution was stirred for an hour. Triisopropyl borate (373.11 g) was added drop wise and reaction was stirred for further an hour. The resulting solution was diluted with aqueous sodium hydroxide and then washed with n-heptane. The pH of the aqueous layer was adjusted to pH 2-3 using hydrochloric acid and then extracted with ethyl acetate. The organic layer was concentrated under vacuum. This was dissolved in ethyl acetate at about 40°C and to this heptane was added to obtain 2- methyl-4-fluorophenylboronic acid. Yield: 61.5%; HPLC purity: 99.00%.

References:

GLENMARK PHARMACEUTICALS LIMITED;KUDUVA, Srinivasan Subramanian;-, Rajender;CHORAGHE, Mahendra Joma;NAIK, Samir;BHIRUD, Shekhar Bhaskar WO2017/125835, 2017, A1 Location in patent:Paragraph 00117

5419-55-6
396 suppliers
$12.00/5g

452-63-1 Synthesis

452-63-1
350 suppliers
$11.00/25g