Cesium carbonate → 3-Chloro-5-fluoromethoxy-pyridine-2-carbonitrile

HRID 221799Notes

Reaction equation

HRID 221799 reaction equation
[Cl:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6]([OH:8])[CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[F:17][CH2:18]OS(C1C=CC(C)=CC=1)(=O)=O>CN(C=O)C>[Cl:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6]([O:8][CH2:18][F:17])[CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 13862289Fluoromethyl 4-methylbenzenesulfonateHCID 666654733-Chloro-5-hydroxypicolinonitrile

Product 1

HCID 666658643-Chloro-5-fluoromethoxy-pyridine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-chloro-5-hydroxy-pyridine-2-carbonitrile (315 mg, 2.03 mmol) in DMF (16 ml) was added Cs2CO3 (1.652 g, 5.07 mmol) and toluene-4-sulfonic acid fluoromethyl ester (CAS registry 114435-86-8) (621 mg, 3.04 mmol) and the reaction mixture was heated at 80° C. for 24 h. The solvent was removed under reduced pressure and the residue taken up in TBME, washed with water and brine, dried over MgSO4, filtered and concentrated. The title compound was obtained as a yellow oil after chromatography on silica gel (hexane-EtOAc 10:1 to 2:1) to provide the title compound as a light yellow oil: TLC (hexane-EtOAc 1:1): Rf=0.62;

Workup

  1. customThe solvent was removed under reduced pressure
  2. washwashed with water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-ac20191e73f345cc9f09b25185f1c199
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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