Triisopropyl borate → (3'-Chloro-3-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)boronic acid

A RBF was charged with 3′-chloro-3-fluoro-5-methoxy-1,1′-biphenyl (513 mg, 2.168 mmol) and THF (7225 μl) to give a clear solution. The flask was cooled in a dry ice-acetone bath for 10 min, then n-butyllithium (1.8M in hexanes) (1445 μA, 2.60 mmol) was added dropwise. After 30 min, triisopropyl borate (597 μl, 2.60 mmol) was added dropwise, and the cooling bath was removed. After 10 min, the mixture was diluted with 2N aq. NaOH, and the resulting biphasic mixture was stirred for 40 min. The mixture was diluted with water and ether. The layers were separated, and the organic layer was extracted with water (1×). The combined aq. extracts were acidified with 2N aq. HCl (30 mL). The resulting suspension was stirred for 20 min then filtered. The collected solid was washed with water (3×), then dried under a stream of N2 (g) for 1 h to give (3′-chloro-3-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)boronic acid (147 mg, 0.524 mmol, 24.18% yield) as an off-white solid. m/z (ESI) 281.0 (M+H)+.

1. customto give a clear solution
2. temperatureThe flask was cooled in a dry ice-acetone bath for 10 min
3. customthe cooling bath was removed
4. waitAfter 10 min
5. additionthe mixture was diluted with 2N aq. NaOH
6. additionThe mixture was diluted with water and ether
7. customThe layers were separated
8. extractionthe organic layer was extracted with water (1×)
9. stirringThe resulting suspension was stirred for 20 min
10. filtrationthen filtered
11. washThe collected solid was washed with water (3×)
12. dry with materialdried under a stream of N2 (g) for 1 h

ORD record

ord-d8b530a485624cb58825de7faa7dd8cb

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09212182B2