Potassium Carbonate → methyl 4-cyclobutyl-5-(5-(methoxymethyl)-1H-imidazol-2-yl)-2-methylbenzoate

HRID 541397Notes

Reaction equation

Br[CH2:2][C:3](=O)[CH2:4][O:5][CH3:6].Cl.[C:9]([C:12]1[C:13]([CH:23]2[CH2:26][CH2:25][CH2:24]2)=[CH:14][C:15]([CH3:22])=[C:16]([CH:21]=1)[C:17]([O:19][CH3:20])=[O:18])(=[NH:11])[NH2:10].C(=O)([O-])[O-].[K+].[K+]>CC#N>[CH:23]1([C:13]2[C:12]([C:9]3[NH:10][C:3]([CH2:4][O:5][CH3:6])=[CH:2][N:11]=3)=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[C:15]([CH3:22])[CH:14]=2)[CH2:24][CH2:25][CH2:26]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a round-bottom flask was added a solution of 1-bromo-3-methoxypropan-2-one (compound 246.2, 505 mg, 1.81 mmol, 1.00 equiv, 60%) in CH3CN (16 mL). Methyl 5-carbamimidoyl-4-cyclobutyl-2-methylbenzoate hydrochloride (compound 245.1, 450 mg, 1.59 mmol, 1.00 equiv) and potassium carbonate (554 mg, 3.61 mmol, 3.00 equiv, 90%) were added to the reaction. The resulting solution was stirred overnight at 80° C. under nitrogen. After cooling to ambient temperature, the reaction was carefully quenched by the addition of water. The resulting mixture was extracted with 2×50 mL of ethyl acetate. The combined organic layers were dried (Na2SO4), and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:2) as eluent to furnish 170 mg (24%) of methyl 4-cyclobutyl-5-(5-(methoxymethyl)-1H-imidazol-2-yl)-2-methylbenzoate as a white solid.

Workup

temperatureAfter cooling to ambient temperature
customthe reaction was carefully quenched by the addition of water
extractionThe resulting mixture was extracted with 2×50 mL of ethyl acetate
dry with materialThe combined organic layers were dried (Na2SO4)
concentrationconcentrated in vacuo
customThe residue was purified

Sources & evidence

ORD record: ord-96c1190ae2454063a1ffcd4e5a5fed66
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871790B2

Reaction notes

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