Potassium Hydroxide → 1-(2-Methoxyethyl)-1H-pyrazole-4-boronic acid, pinacol ester

HRID 2366902Notes

Reaction equation

[CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.[OH-].[K+].Br[CH2:18][CH2:19][O:20][CH3:21]>C(O)C>[CH3:21][O:20][CH2:19][CH2:18][N:12]1[CH:13]=[C:9]([B:4]2[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]2)[CH:10]=[N:11]1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (10 g, 51.5 mmol) in ethanol (50 mL) was treated with KOH (3.47 g, 61.8 mmol) and 1-bromo-2-(methyloxy)ethane (5.81 mL, 61.8 mmol) at room temperature and the resulting mixture was stirred at 50° C. under nitrogen for 16 h then cooled to room temperature. 1-Bromo-2-(methyloxy)ethane (2 mL, 21.3 mmol) was added and the resulting mixture was stirred at 50° C. for 60 h then cooled to room temperature. The mixture was filtered through celite and the insoluble were washed with ethanol. The combined filtrate and washings were concentrated in vacuo. Purification of the residue on SP4 using a 100 G silica cartridge (gradient: 0 to 100% AcOEt in Hexanes) gave 1-[2-(methyloxy)ethyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.72 g, 10.25 mmol, 20%) as a yellow oil. LCMS (method G): Retention time 0.87 min, [M+H]+=252.9

Workup

temperaturethen cooled to room temperature
stirringthe resulting mixture was stirred at 50° C. for 60 h
temperaturethen cooled to room temperature
filtrationThe mixture was filtered through celite
washthe insoluble were washed with ethanol
concentrationThe combined filtrate and washings were concentrated in vacuo
customPurification of the residue on SP4

Sources & evidence

ORD record: ord-6bb976d6acf349049cff7ff36dac8106
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697725B2

Reaction notes

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