Sodium Nitrite → 3-[1-ethyl-5-(4-fluorophenoxy)-1H-pyrazol-3-yl]benzonitrile

HRID 540759Notes

Reaction equation

N[C:2]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[N:9]([CH2:10][CH3:11])[N:8]=[C:7]([C:12]2[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=2)[C:15]#[N:16])[CH:6]=1.N([O-])=O.[Na+]>Cl.O>[CH2:10]([N:9]1[C:5]([O:4][C:3]2[CH:2]=[CH:23][C:22]([F:24])=[CH:21][CH:20]=2)=[CH:6][C:7]([C:12]2[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=2)[C:15]#[N:16])=[N:8]1)[CH3:11]

Participants

Conditions

Temperature: 22 °C

Procedure

3-[5-(2-amino-4-fluorophenoxy)-1-ethyl-1H-pyrazol-3-yl]benzonitrile (0.25 g, 0.78 mmol, 1 equiv) was dissolved in a mixture of 1:1 36% aq HCl: 50% aq hypophosphoric (12.7 mL) acid and then cooled to −5° C. Sodium nitrite (3 M in water, 0.27 g, 3.88 mmol, 5 equiv) was added dropwise. The resulting mixture was warmed to 22° C. and stirred for 1 hr. The mixture was then diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride then dried over anhydrous magnesium sulfate. The drying agent was filtered and the filtrate was concentrated in vacuo. The residue (0.24 g) was purified by flash-column chromatography on silica gel (0-45% EtOAc:Hex) to give 3-[1-ethyl-5-(4-fluorophenoxy)-1H-pyrazol-3-yl]benzonitrile. Calcd (M+1)+: 308.1. Found 308.0.

Workup

extractionextracted with ethyl acetate
washThe organic layer was washed with saturated aqueous sodium chloride
dry with materialthen dried over anhydrous magnesium sulfate
filtrationThe drying agent was filtered
concentrationthe filtrate was concentrated in vacuo
customThe residue (0.24 g) was purified by flash-column chromatography on silica gel (0-45% EtOAc:Hex)

Sources & evidence

ORD record: ord-ce1664d9a37649d184529cdec715f822
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871796B2

Reaction notes

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