Sodium hydride → 3,5-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole

HRID 885908Notes

Reaction equation

HRID 885908 reaction equation
[CH3:1][C:2]1[C:6]([B:7]2[O:11][C:10]([CH3:13])([CH3:12])[C:9]([CH3:15])([CH3:14])[O:8]2)=[C:5]([CH3:16])[NH:4][N:3]=1.[H-].[Na+].Cl[CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25]>C1COCC1>[CH3:1][C:2]1[C:6]([B:7]2[O:11][C:10]([CH3:12])([CH3:13])[C:9]([CH3:15])([CH3:14])[O:8]2)=[C:5]([CH3:16])[N:4]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[N:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 162177133,5-Dimethylpyrazole-4-boronic acid, pinacol ester

Product 1

HCID 671878743,5-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazoleYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred suspension of 3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.15 g, 0.68 mmol) in THF (5 mL) was treated with NaH (0.032 g, 60% dispersion in oil, 0.81 mmol) at r.t. After 5 minutes [2-(chloromethoxy)ethyl]-trimethylsilane (0.14 mL, 0.81 mmol) was added and the reaction mixture stirred for 1.5 h. The reaction mixture was quenched with water (5 mL), diluted with EtOAc (20 mL) and the organic fraction separated. The organic fraction was dried (MgSO4), filtered and concentrated in vacuo. Purification by column chromatography (SiO2, 0-40% EtOAc/hexanes) gave the title compound (0.206 g, 86%) as a clear oil. δH (CDCl3) 5.35 (2H, s), 3.60 (2H, m), 2.50 (3H, s), 2.35 (3H, s), 1.35 (12H, s), 0.90 (2H, m), 0.00 (9H, s). LCMS (ES+) 353.0 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with water (5 mL)
  2. additiondiluted with EtOAc (20 mL)
  3. customthe organic fraction separated
  4. dry with materialThe organic fraction was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by column chromatography (SiO2, 0-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-91d8a95eb68a487eb652ef42a3c7a7c3
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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