Ethyl Acetate → 1,3,5-Trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

HRID 1988135Notes

Reaction equation

HRID 1988135 reaction equation
Br[C:2]1[C:3]([CH3:9])=[N:4][N:5]([CH3:8])[C:6]=1[CH3:7].C([Li])CCC.C(O[B:19]1[O:23][C:22]([CH3:25])([CH3:24])[C:21]([CH3:27])([CH3:26])[O:20]1)(C)C.C(OCC)(=O)C>C1COCC1>[CH3:8][N:5]1[C:6]([CH3:7])=[C:2]([B:19]2[O:23][C:22]([CH3:25])([CH3:24])[C:21]([CH3:27])([CH3:26])[O:20]2)[C:3]([CH3:9])=[N:4]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 5191814-Bromo-1,3,5-trimethylpyrazoleHCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 178418339Butyllithium

Product 1

HCID 27953111,3,5-Trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleYield 79.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-bromo-1,3,5-trimethyl-1H-pyrazole (1 g, 5.3 mmol) in anhydrous THF (20 mL) cooled to −78° C. under a nitrogen atmosphere was treated dropwise with n-butyl lithium (4.2 mL, 1.6 M in hexane) and stirred at room temperature for 20 minutes. Then, 2-isopropoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (1.7 mL, 8.3 mmol) was added dropwise at −78° C. and allowed to warm to ambient temperature overnight. Ethyl acetate was added and the mixture was filtered through diatomaceous earth. The filtrate was concentrated and chromatographed on silica gel eluting with 40% ethyl acetate in hexanes to provide the title compound as white crystals (996 mg, 77%). 1H NMR (300 MHz, CDCl3) δ 1.29 (s, 12 H), 2.33 (s, 3 H), 2.37 (s, 3 H), 3.69 (s, 3 H); (DCl/NH3) m/z 237 (M+H)+.

Workup

  1. temperatureto warm to ambient temperature overnight
  2. filtrationthe mixture was filtered through diatomaceous earth
  3. concentrationThe filtrate was concentrated
  4. customchromatographed on silica gel eluting with 40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-72c96332215b4ac195f08bfd7b6913d0
Source dataset
uspto-grants-2009_06
Patent number
US07553964B2

Reaction notes

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