Water → 6-(2,4-Difluorophenoxy)-2-methylnicotinonitrile

HRID 1620406Notes

Reaction equation

Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([CH3:10])[N:3]=1.[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[OH:19].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[O:19][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([CH3:10])[N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 6-chloro-2-methylnicotinonitrile (Example 1, step 1; 500 mg, 3.27 mmol), 2,4-difluorophenol (0.47 mL, 4.91 mmol) and cesium carbonate (1.60 g, 4.91 mmol) in DMF (5 mL) was heated in an oil bath at 80° C. for 5 h. The reaction mixture was treated with water and extracted with EtOAc (2×20 mL). The combined organic layers were washed with 1 N NaOH (15 mL) followed by brine, dried over MgSO4 and concentrated. Purification on an ISCO (40 g column, 5-50% EtOAc in hexanes) provided 6-(2,4-difluorophenoxy)-2-methylnicotinonitrile as a white crystalline solid. MS (ESI, pos.ion) m/z: M+1=247.0

Workup

extractionextracted with EtOAc (2×20 mL)
washThe combined organic layers were washed with 1 N NaOH (15 mL)
dry with materialdried over MgSO4
concentrationconcentrated
customPurification on an ISCO (40 g column, 5-50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-47ad884e09a848a7be10552e10dcd842
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772481B2

Reaction notes

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