Tributyl borate → (5-Isopropyl-1H-indazol-4-yl)boronic acid

HRID 251582Notes

Reaction equation

Br[C:2]1[C:10]([CH:11]([CH3:13])[CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[Li]C(C)(C)C.[B:19](OCCCC)([O:25]CCCC)[O:20]CCCC>CCOCC>[CH:11]([C:10]1[CH:9]=[CH:8][C:7]2[NH:6][N:5]=[CH:4][C:3]=2[C:2]=1[B:19]([OH:25])[OH:20])([CH3:13])[CH3:12]

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of 4-bromo-5-isopropyl-1H-indazole (116 g, 6.9 mmol) in Et2O (4 mL) is added slowly to a suspension of KH (1.0 g of 30% dispersion in mineral oil, 7.7 mmol) in Et2O (20 mL) at 0° C. and the mixture is stirred for 20 minutes. After cooling to −78° C., t-BuLi (8.9 mL of 1.7 M in Hex, 15 mmol) is added and the resulting mixture is stirred for 40 minutes at −78° C. To this is added B(On-Bu)3 (5.6 mL, 21 mmol) and the mixture is stirred for 24 hours at room temperature. The reaction mixture is quenched with 1N H3PO4 and extracted with Et2O— The combined Et2O layers are back-extracted with 1N NaOH (3×10 mL). The combined NaOH extracts are acidified with 1N H3PO4 and extracted with EtOAc. The EtOAc extracts are washed with saturated brine, dried (MgSO4), and concentrated to yield 5-isopropyl-1H-indazole-4-boronic acid. 1H NMR (CDCl3) 7.85 (s, 1H), 7.42 (d, 1H), 7.37 (d, 1H), 3.6 (br s, 2H), 2.88 (m, 1H), 1.32 (d, 6H).

Workup

stirringthe resulting mixture is stirred for 40 minutes at −78° C
stirringthe mixture is stirred for 24 hours at room temperature
customThe reaction mixture is quenched with 1N H3PO4
extractionextracted with Et2O— The combined Et2O layers
extractionare back-extracted with 1N NaOH (3×10 mL)
extractionextracted with EtOAc
washThe EtOAc extracts are washed with saturated brine
dry with materialdried (MgSO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-23c66020eaa84ed5b99454314f54f220
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07863454B2

Reaction notes

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