Carbon Dioxide → 3,5-Dichloropyrazine-2-carboxylic acid

HRID 917607Notes

Reaction equation

HRID 917607 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[Cl:13][C:14]1[CH:19]=[N:18][CH:17]=[C:16]([Cl:20])[N:15]=1.[C:21](=[O:23])=[O:22]>O1CCCC1.CCCCCC.CC(C)=O.Cl>[C:21]([C:17]1[C:16]([Cl:20])=[N:15][C:14]([Cl:13])=[CH:19][N:18]=1)([OH:23])=[O:22]

Participants

9

Reactant 4

HCID 280Carbon DioxideHCID 7912DiisopropylamineHCID 785042,6-DichloropyrazineHCID 178418339Butyllithium

Product 1

HCID 226655363,5-Dichloropyrazine-2-carboxylic acid

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of diisopropylamine (0.78 g) in tetrahydrofuran (40 ml) is dropped a 1.6M solution of n-butyl lithium in hexane (4.82 ml) over a period of 3 minutes under cooling on dry ice in acetone bath. The mixture is stirred on the same bath for 30 minutes and thereto is added 2,6-dichloropyrazine 0.50 g in tetrahydrofuran 5 ml at the same temperature over a period of 15 minutes. After stirring for 1 hour, the mixture is poured into dry ice and stirred at room temperature for 1 hour. The mixture is diluted with 10% hydrochloric acid to be adjusted pH about 2 and extracted with ethyl acetate. The combined organic layer is extracted with an aqueous saturated sodium hydrogen carbonate solution. The water extract is washed with ethyl acetate and made acid with a 10% aqueous hydrochloric acid solution and extracted with ethyl acetate. The combined organic layer is washed with water and an aqueous saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The residue is titrated with chloroform-hexane (1:1) to give 2-carboxy-3,5-dichloropyrazine 234 mg as a slightly brownish crystalline powder. mp 139-141° C., MS(m/z): 191 (M−H)−

Workup

  1. stirringAfter stirring for 1 hour
  2. stirringstirred at room temperature for 1 hour
  3. extractionextracted with ethyl acetate
  4. extractionThe combined organic layer is extracted with an aqueous saturated sodium hydrogen carbonate solution
  5. extractionThe water extract
  6. washis washed with ethyl acetate
  7. extractionextracted with ethyl acetate
  8. washThe combined organic layer is washed with water
  9. dry with materialan aqueous saturated sodium chloride solution, dried over sodium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-92fbb21d0eaf48f586418e0a52d2d04d
Source dataset
uspto-grants-2007_09
Patent number
US07273868B2

Reaction notes

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