Toluene → 6-cyclopropyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole

HRID 245804

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.[CH:19]1(B(O)O)[CH2:21][CH2:20]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH:19]1([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[N:7][N:8]3[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=2)[CH2:21][CH2:20]1

Participants

Conditions

Temperature: 100 °C

Procedure

A round-bottomed flask was charged with 6-bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole (0.80 g, 2.44 mmol), cyclopropylboronic acid (377 mg, 4.39 mmol), palladium(II) acetate (28 mg, 0.125 mmol), potassium phosphate tribasic (1.04 g, 4.88 mmol), toluene (9 ml) and water (0.9 ml). The reaction mixture was stirred at 100° C. in an oil bath overnight then cooled to room temperature, quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/Hexanes (gradient 0-5% EtOAc) to afford 670 mg (90%) of 6-cyclopropyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole as a light yellow oil.

Workup

temperaturethen cooled to room temperature
customquenched with water
extractionextracted with EtOAc (2×)
washThe combined organic layers were washed with water and brine
dry with materialthen dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was chromatographed over silica gel with EtOAc/Hexanes (gradient 0-5% EtOAc)

Sources & evidence

ORD record: ord-c18be89c1d6c4caba5d0593ea777c4b6
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Linked notes

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