Tert-Butyl nitrite → HCID 67111062, compound

HRID 540756Notes

Reaction equation

HRID 540756 reaction equation
N[C:2]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:9]=[C:8]([C:10]2[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=2)[C:13]#[N:14])[N:7]([CH2:18][CH3:19])[N:6]=1.C(ON=O)(C)(C)C>CN(C)C=O>[CH2:18]([N:7]1[C:8]([C:10]2[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=2)[C:13]#[N:14])=[CH:9][C:5]([O:4][C:3]2[CH:2]=[CH:23][C:22]([F:24])=[CH:21][CH:20]=2)=[N:6]1)[CH3:19]

Participants

4

Reactant 2

HCID 10906Tert-Butyl nitriteHCID 67111714HCID 67111714, compound

Product 1

HCID 67111062HCID 67111062, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 3-[3-(2-amino-4-fluorophenoxy)-1-ethyl-1H-pyrazol-5-yl]benzonitrile (262 mg, 0.813 mmol, 1 equiv) in N,N-dimethylformamide (2 mL) was added dropwise over 5 minutes to a solution of t-butylnitrite (0.15 mL, 1.2 mmol, 1.5 equiv) in N,N-dimethylformamide (2.5 mL) at 60° C. The reaction mixture was stirred at 60° C. for 20 minutes, then was partitioned between ethyl acetate and aqueous hydrochloric acid solution (1 M). The organic layer was washed sequentially with an additional portion of aqueous hydrochloric acid solution (1 M) and saturated aqueous sodium chloride solution. The washed organic layer was dried over sodium sulfate, and the dried solution was filtered. The filtrate was concentrated, and the residue was purified by flash-column chromatography on silica gel (hexanes, grading to 50% ethyl acetate-hexanes) to afford 3-[1-ethyl-3-(4-fluorophenoxy)-1H-pyrazol-5-yl]benzonitrile (127 mg, 51%) as a white solid. Calcd (M+1)+: 308.1. Found: 308.0.

Workup

  1. customwas partitioned between ethyl acetate and aqueous hydrochloric acid solution (1 M)
  2. washThe organic layer was washed sequentially with an additional portion of aqueous hydrochloric acid solution (1 M) and saturated aqueous sodium chloride solution
  3. dry with materialThe washed organic layer was dried over sodium sulfate
  4. filtrationthe dried solution was filtered
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by flash-column chromatography on silica gel (hexanes, grading to 50% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-09891c22581b48f4a5630caa01774ee3
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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