Cesium carbonate → 1-(2-Methoxyethyl)-1H-pyrazole-4-boronic acid, pinacol ester

HRID 877430Notes

Reaction equation

HRID 877430 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.Cl[CH2:16][CH2:17][O:18][CH3:19].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH3:19][O:18][CH2:17][CH2:16][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

5

Reactant 3

HCID 10796Cesium carbonateHCID 123162-Chloroethyl methyl etherHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 112304911-(2-Methoxyethyl)-1H-pyrazole-4-boronic acid, pinacol esterYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (100 mg, 0.52 mmol), 1-chloro-2-methoxyethane (0.056 mL, 0.62 mmol) and cesium carbonate (252 mg, 0.73 mmol) in DMF (1 mL) were heated in microwave reactor at 160° C. for 30 min. The reaction mixture was concentrated under reduced pressure and purified by silica gel chromatography (ISCO, hexanes/ethyl acetate 0-100% over 15 min) to isolate Compound B162a (130 mg, 100% yield). HPLC: RT=1.0 min (LCMS Method M). MS (ES): m/z=253.0 [M+H]+. 1H NMR (500 MHz, CHLOROFORM-d) δ 8.04 (s, 1H), 7.83 (d, J=18.4 Hz, 1H), 4.37 (t, J=5.2 Hz, 1H), 3.78 (t, J=5.2 Hz, 1H), 3.38-3.31 (m, 2H), 2.98 (s, 3H), 2.90 (s, 3H), 1.34 (s, 6H), 1.26 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. custompurified by silica gel chromatography (ISCO, hexanes/ethyl acetate 0-100% over 15 min)
  3. customto isolate Compound B162a (130 mg, 100% yield)

Sources & evidence

ORD record
ord-80a4bf554dea44bfb2cebed8a18b35d7
Source dataset
uspto-grants-2015_03
Patent number
US08987314B2

Reaction notes

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