4-Aminophenol → HCID 131733314, compound

HRID 515901Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Cl[C:10]1[N:15]=[C:14]([C:16]#[N:17])[CH:13]=[CH:12][CH:11]=1.N1C=CN=C1.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>CN1CCCC1=O.O>[Si:23]([O:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:10]2[N:15]=[C:14]([C:16]#[N:17])[CH:13]=[CH:12][CH:11]=2)=[CH:3][CH:4]=1)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]

Participants

Conditions

Temperature: 145 °C

Procedure

4-Aminophenol (3.3 g, 30.2 mmol) is added to a solution of 6-chloropyridine-2-carbonitrile (3.5 g, 25.3 mmol) in 1-methyl-2-pyrrolidinone (70 mL). The reaction mixture is heated at 140-150° C. for 16 hours in a sealed flask. The batch is then cooled to ambient temperature. Imidazole (3.4 g, 49.9 mmol) and tert-butyl(dimethyl)silyl chloride (7.6 g, 50.4 mmol) are subsequently added and the mixture is stirred for 16 hours at ambient temperature. The mixture is diluted with water (140 mL) and the product is extracted with AcOEt (4×50 mL). The organic phases are combined and washed with water (3×50 mL), and then brine (1×50 mL). The organic phase is then dried over MgSO4, filtered and concentrated in vacuo. The crude product is purified by chromatography over silica gel using ethyl acetate and heptane as eluants to obtain the title product.

Workup

temperatureThe batch is then cooled to ambient temperature
extractionthe product is extracted with AcOEt (4×50 mL)
washwashed with water (3×50 mL)
dry with materialThe organic phase is then dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product is purified by chromatography over silica gel

Sources & evidence

ORD record: ord-4f7fc03deec84e33aef3cbb33598a0b3
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108983B2

Reaction notes

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