Imidazole → 4-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-2-chloro-5-methoxyaniline

HRID 630385Notes

Reaction equation

[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([CH2:9][OH:10])=[C:4]([O:11][CH3:12])[CH:3]=1.N1C=CN=[CH:14]1.Cl[Si:19]([CH:22]([CH3:24])[CH3:23])([CH3:21])[CH3:20]>CN(C)C=O>[Si:19]([O:10][CH2:9][C:5]1[C:4]([O:11][CH3:12])=[CH:3][C:2]([NH2:1])=[C:7]([Cl:8])[CH:6]=1)([C:22]([CH3:24])([CH3:14])[CH3:23])([CH3:21])[CH3:20]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (4-amino-5-chloro-2-methoxyphenyl)methanol (intermediate 38; 1.5 g, 0.008 mol) in dimethylformamide (35 mL) was added imidazole (1.7 g, 0.02 mol). The mixture was cooled to 0° C. and chloro(isopropyl)dimethylsilane (2.5 g, 0.01 mol) was added dropwise. The reaction was stirred overnight at room temperature. The solvent was removed and the crude was partitioned between water and hexane, the organic layer was washed with water, sodium bicarbonate 4% and brine, dried, filtered and evaporated to dryness. The crude obtained was purified by column chromatography with silica gel, eluting with hexane/ethyl acetate (from 8/1 to 4/1). The title compound was obtained as a yellow solid (58%).

Workup

customThe solvent was removed
customthe crude was partitioned between water and hexane
washthe organic layer was washed with water, sodium bicarbonate 4% and brine
customdried
filtrationfiltered
customevaporated to dryness
customThe crude obtained
customwas purified by column chromatography with silica gel
washeluting with hexane/ethyl acetate (from 8/1 to 4/1)

Sources & evidence

ORD record: ord-3059ad39c35c425c99e98cab15a03848
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315463B2

Reaction notes

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