Triisopropyl borate → [3-Chloro-4-(trifluoromethoxy)phenyl]boronic acid

Temperature

-78 °C

Triisopropylborate (0.76 mL, 3.29 mmol) and iodide 54 (815 mg, 2.53 mmol) were successively added via syringe to a mixture of anhydrous toluene (4 mL) and anhydrous distilled THF (1 mL) under N2 and the mixture was cooled to −78° C. n-Butyllithium (1.08 mL of a 2.5 M solution in hexanes, 2.70 mmol) was added drop-wise over 75 min to the stirred solution (at −78° C.), and the mixture was stirred at −78° C. for an additional 3 h, and then slowly warmed to −20° C. (over 1.5H). 2N HCl (2.6 mL) was added and the mixture was stirred at room temperature for 30 min, and then diluted with water (40 mL) and extracted with EtOAc (5×50 mL). The extracts were washed with brine (50 mL) and then evaporated to dryness. The residue was triturated in pentane (˜3-4 mL), cooled to −78° C., and rapidly filtered cold (washing with pentane cooled to −78° C.) to give 3-chloro-4-(trifluoromethoxy)phenylboronic acid (55) (459 mg, 76%) as a white solid (a 1:1 mixture of the trimeric boroxine and the boronic acid by NMR): mp 202-204° C.; 1H NMR (CDCl3) δ 8.26 (d, J=1.5 Hz, 3H, boroxine), 8.12 (dd, J=8.2, 1.5 Hz, 3H, boroxine), 7.85 (d, J=1.5 Hz, 1H, boronic acid), 7.65 (dd, J=8.2, 1.6 Hz, 1H, boronic acid), 7.48 (dq, J=8.2, 1.5 Hz, 3H, boroxine), 7.35 (dq, J=8.2, 1.5 Hz, 1H, boronic acid), 4.57 (s, 2H, boronic acid).

1. distillationanhydrous distilled THF (1 mL) under N2
2. additionwas added drop-wise over 75 min to the stirred solution (at −78° C.)
3. temperatureslowly warmed to −20° C. (over 1.5H)
4. addition2N HCl (2.6 mL) was added
5. stirringthe mixture was stirred at room temperature for 30 min
6. additiondiluted with water (40 mL)
7. extractionextracted with EtOAc (5×50 mL)
8. washThe extracts were washed with brine (50 mL)
9. customevaporated to dryness
10. customThe residue was triturated in pentane (˜3-4 mL)
11. temperaturecooled to −78° C.
12. washrapidly filtered cold (washing with pentane cooled to −78° C.)

ORD record

ord-3fd1922574bb4725a64acaf2ab117d3f

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09198913B2