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

HRID 431056Notes

Reaction equation

HRID 431056 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.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

8

Reactant 4

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

Product 1

HCID 226655363,5-Dichloropyrazine-2-carboxylic acid

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of diisopropylamine (0.78 g) in tetrahydrofuran (40 ml) is added dropwise a 1.6M solution of n-butyl lithium in hexane (4.82 ml) in a dry ice-acetone bath over a period of 3 minutes. The mixture is stirred in the same bath for 30 minutes. To the mixture is added dropwise a solution of 2,6-dichloropyrazine (0.50 g) in tetrahydrofuran (5 ml) at the same temperature over a period of 15 minutes, and the mixture is stirred for one hour. The reaction mixture is poured into dry ice, and the mixture is stirred at room temperature for one hour. The reaction mixture is diluted with a 10% aqueous hydrochloric acid solution in order to adjust the pH value thereof to about 2, and then extracted with ethyl acetate. The combined organic layers are extracted with a saturated aqueous sodium hydrogen carbonate solution, and the aqueous extract is washed with ethyl acetate, acidified with a 10% aqueous hydrochloric acid, and extracted with ethyl acetate. The combined organic layer is washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is triturated with a mixture of chloroform and hexane (1:1) to give 2-carboxy-3,5-dichloropyrazine (234 mg) as a slightly brown crystalline powder, m.p. 139-141° C., MS (m/z): 191 (M−H)−.

Workup

  1. stirringthe mixture is stirred for one hour
  2. stirringthe mixture is stirred at room temperature for one hour
  3. extractionto about 2, and then extracted with ethyl acetate
  4. extractionThe combined organic layers are extracted with a saturated aqueous sodium hydrogen carbonate solution
  5. extractionthe aqueous extract
  6. washis washed with ethyl acetate
  7. extractionextracted with ethyl acetate
  8. washThe combined organic layer is washed with water
  9. dry with materiala saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue is triturated with a mixture of chloroform and hexane (1:1)

Sources & evidence

ORD record
ord-31837a71fe10419ba938b261a1893edc
Source dataset
uspto-grants-2003_12
Patent number
US06656935B2

Reaction notes

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