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

HRID 606298

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 (1.6 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
extractionThe combined Et2O layers are 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-12ec9a4449c94a90a29fe17d4c70fed1
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07915288B2

Linked notes

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