Triisopropyl borate → (5-Bromo-2-cyclopropylphenyl)boronic acid

To a solution of 5-bromo-2-cyclopropyliodobenzene (5.67 g, 0.018 mol) in anhydrous tetrahydrofuran (32 ml) at −78° C. is added isopropylmagnesium chloride (9.5 ml, 0.019 mol, 2M solution in THF) at such a rate as to maintain a temperature below −60° C. Once addition is complete the reaction mixture is stirred for 20 minutes at this temperature and then allowed to warm to room temperature and stir for an additional 2 hours. The solution is then cooled again to −78° C. and triisopropylborate (8.3 ml, 0.036 mol) is added dropwise. After stirring at this temperature for 10 minutes the solution is allowed to warm to room temperature and stir for an additional 2 hours. After quenching with 2M aqueous hydrochloric acid (20 ml) the reaction mixture is dilluted with distilled water then extracted with ethyl acetate (×3). Organic fractions are combined, washed with distilled water and brine, then dried over magnesium sulfate and concentrated in vacuo. The crude solid is azeotroped with toluene (×3) then triturated with isohexane to afford 5-bromo-2-cyclopropylphenyl boronic acid as a cream solid.

1. temperatureto maintain a temperature below −60° C
2. additionOnce addition
3. stirringstir for an additional 2 hours
4. temperatureThe solution is then cooled again to −78° C.
5. stirringAfter stirring at this temperature for 10 minutes the solution
6. temperatureto warm to room temperature
7. stirringstir for an additional 2 hours
8. customAfter quenching with 2M aqueous hydrochloric acid (20 ml) the reaction mixture
9. extractionthen extracted with ethyl acetate (×3)
10. washwashed with distilled water and brine
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated in vacuo
13. customThe crude solid is azeotroped with toluene (×3)
14. customthen triturated with isohexane

ORD record

ord-5819ca3a0ea949bfb01787ed835847c6

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895474B2