Hydrochloric Acid → 4-Cyanophenylboronic acid

Temperature

-100 °C

A solution of 4-bromobenzonitrile (91 g, 0.50 mole) in THF (1.1 L) was dried in the presence of activated 3 Å molecular sieves at room temp. This solution was filtered and cooled to −100° C. A 1.6 M solution of n-butyllithium in hexanes (355 mL. 0.567 mol) was added to the cold solution over 15 min while maintaining the internal temperature between −105 and −93° C. To the resulting orange reaction mixture was added trimethylborate (81 g, 0.78 mol) over 3 min, briefly increasing the reaction temperature to −72° C. The reaction mixture was recooled to −100° C. over 5 minutes and then was allowed to warm slowly to room temperature over 2.3 h. The reaction mixture was acidified with 4N HCl to pH 2.2, and was diluted with CH2Cl2 (200 mL). The aqueous layer was separated and the organic layer was washed with brine (2×200 mL), dried over anhydrous MgSO4, filtered, and the solvent removed under reduced pressure to a pale yellow solid. This solid was additionally purified by dissolution in 1N NaOH and extraction into CH2Cl2/THF (1:1, 2×200 mL). The aqueous phase was acidified with 4N HCl to pH 2.2 and was extracted into CH2Cl2/THF (1:1, 500 mL). The combined organic extracts were concentrated to a crude solid (64.6 g) that was triturated with diethyl ether (160 mL) and dried under vacuum to afford the intermediate title compound (44.0 g, 59.9%) as a white powder. 1H NMR (d6-acetone, 300 MHz): δ 8.03 (d, 2H, J=8.1), 7.75 (d, 2H, J=8.4), 7.54 (s, 2H).

1. filtrationThis solution was filtered
2. temperaturewhile maintaining the internal temperature between −105 and −93° C
3. temperaturebriefly increasing the reaction temperature to −72° C
4. temperatureto warm slowly to room temperature over 2.3 h
5. customThe aqueous layer was separated
6. washthe organic layer was washed with brine (2×200 mL)
7. dry with materialdried over anhydrous MgSO4
8. filtrationfiltered
9. customthe solvent removed under reduced pressure to a pale yellow solid
10. customThis solid was additionally purified by dissolution in 1N NaOH
11. extractionextraction into CH2Cl2/THF (1:1, 2×200 mL)
12. extractionwas extracted into CH2Cl2/THF (1:1, 500 mL)
13. concentrationThe combined organic extracts were concentrated to a crude solid (64.6 g) that
14. customwas triturated with diethyl ether (160 mL)
15. customdried under vacuum

ORD record

ord-fc61e3e1ce1c475bb49e5b791d865de9

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06800651B2