Diethyl Ether → Methyl 3-(trifluoromethyl)pyrazine-2-carboxylate

HRID 535785Notes

Reaction equation

HRID 535785 reaction equation
I[C:2]1[C:3]([C:8]([O:10][CH3:11])=[O:9])=[N:4][CH:5]=[CH:6][N:7]=1.Cl[C:13]([F:19])([F:18])C(OC)=O.[F-:20].[K+].C(OCC)C>CN(C=O)C.[Cu](Cl)Cl>[F:18][C:13]([F:19])([F:20])[C:2]1[C:3]([C:8]([O:10][CH3:11])=[O:9])=[N:4][CH:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 73935Methyl chlorodifluoroacetateHCID 522689Potassium FluorideHCID 57681180Methyl 3-iodopyrazine-2-carboxylate

Product 1

HCID 58542464Methyl 3-(trifluoromethyl)pyrazine-2-carboxylateYield 41%

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To methyl 3-iodopyrazine-2-carboxylate (7) (10 g, 37.88 mmol) in DMF (Volume: 300 mL) was added methyl chlorodifluoroacetate (27 g, 0.189 mol), potassium fluoride (13.2 g, 0.227 mol), and copper chloride (22.47 g., 0.227 mol). The reaction was heated at 120° C. for 12 h. The reaction mixture was poured into ethyl ether (1000 ml) and washed with brine (3×300 ml), dried over MgSO4 before the solvent was removed. The residue was loaded onto a silica column and was eluted using ethyl acetate/hexanes gradient to afford the title compound (3.19 g, 41%) as an amber oil: 1H NMR (400 MHz, CDCl3) δ 8.85 (d, J=5.4 Hz, 1H), 8.82 (d, J=5.4 Hz, 1H), 4.05 (s, 3H); EIMS m/z 206.

Workup

  1. washwashed with brine (3×300 ml)
  2. dry with materialdried over MgSO4 before the solvent
  3. customwas removed
  4. washwas eluted

Sources & evidence

ORD record
ord-63bf36e5f48d40acb54f35fe0f53d70e
Source dataset
uspto-grants-2014_10
Patent number
US08859558B2

Reaction notes

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