Potassium Carbonate → 1-(methoxymethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

HRID 2366884Notes

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.[CH3:15][O:16][CH2:17]I.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH3:15][O:16][CH2:17][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: 35 °C

Procedure

4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (10.00 g, 51.5 mmol) was dissolved in acetonitrile (40 mL) and stirred at 35° C. for 5 min under nitrogen atmosphere then cooled to room temperature. Iodomethyl methyl ether (21.83 mL, 258 mmol) and potassium carbonate (35.6 g, 258 mmol) were added and the resulting mixture was stirred at 35° C. for 3 h then cooled to room temperature. The insoluble material was filtered off and the filtrate was concentrated in vacuo. The residue was dissolved in EtOAc and the organic phase was washed with water, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 100 G silica cartridge (gradient: 0 to 50% AcOEt in hexanes) gave 1-[(methyloxy)methyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (6.45 g, 50% pure by LCMS, 26%) as a yellow liquid which was used in the next step without further purification.

Workup

temperaturethen cooled to room temperature
stirringthe resulting mixture was stirred at 35° C. for 3 h
temperaturethen cooled to room temperature
filtrationThe insoluble material was filtered off
concentrationthe filtrate was concentrated in vacuo
dissolutionThe residue was dissolved in EtOAc
washthe organic phase was washed with water
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customPurification of the residue by SP4

Sources & evidence

ORD record: ord-a0c8673b16564f298e54b7e6561851b5
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697725B2

Reaction notes

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