2-(4-Fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic acid synthesis

Yield:1255945-85-7 65%

Reaction Conditions:

with water;lithium hydroxide in tetrahydrofuran at 20; for 4 h;

Steps:

7.A.3 Step-3

Step-3 [0392] Boronate ester form step-2 was dissolved in mix of Water and solvents like THF/methanol/Acetone that are miscible in water. To this, lithium hydroxide was added and mixture was stirred at room temperature and monitored by TLC & LCMS till maximum starting was consumed (6-12 hrs required) THF was then concentrated and reaction mass was extracted with ethyl acetate and water. Organic layer was washed with water and combined aq. washings were acidified with 2N HCl and extracted with ethyl acetate. Ethyl acetate extract was dried over sodium sulphate and concentrated in vacuum to get crude product. In most of the cases products were sufficient pure to be used for the next step. The details of compounds synthesized by above method are as below. [0393] The details of compounds synthesized are as below in Table 12. LiOH (3.0 eq.), THF:H2O (1:1), RT, 4 h, 65%.

References:

US2014/194383,2014,A1 Location in patent:Paragraph 0387; 0392-0393