Carbon Dioxide → phenyl N-(5-chloro-1-methylpyrazin-2-on-3-yl)-carbamate

HRID 1381468Notes

Reaction equation

HRID 1381468 reaction equation
[NH2:1][C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Cl:8])[N:7]=1.[H-].[Na+].[C:13](=O)([O:21]C1C=CC=CC=1)[O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)=O.Cl>CN(C)C=O.O1CCCC1.ClCCl>[Cl:8][C:6]1[N:7]=[C:2]([NH:1][C:13](=[O:21])[O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=1

Participants

9

Reactant 5

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 7597Diphenyl carbonateHCID 24758Sodium hydrideHCID 130629753-amino-5-chloro-1-methyl-2(1H)-pyrazinone

Product 1

HCID 14350431phenyl N-(5-chloro-1-methylpyrazin-2-on-3-yl)-carbamate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-amino-5-chloro-1-methyl-2(1H)-pyrazinone (11.17 g, 0.070 mol) in anhydrous N,N-dimethylformamide (90 mL) was treated with oil-free sodium hydride (3.4 g, 0.154 mol). After stirring at room temperature for 1 hour, the mixture was cooled with the aid of a dry ice-acetone bath while a solution of diphenyl carbonate (16.49 g, 0.077 mol) in N,N-dimethylformamide (60 mL) was added as rapidly as possible. A wet ice bath was substituted for the dry ice bath, and the reaction mixture was stirred at approximately 0° C. for 3 hours. The mixture was allowed to briefly warm to room temperature, and was then poured into a stirred mixture of ice (350 g), concentrated hydrochloric acid (42 mL); dichloromethane (318 mL), and tetrahydrofuran (32 mL). The layers were separated, and the aqueous layer was extracted with 10:1 dichloromethane-tetrahydrofuran (5×100 mL). The combined organic solutions were dried (Na2SO4), and the solvent was rotary evaporated. After the residue was taken up in toluene, further rotary evaporation left a tan solid. This solid was taken up in dichloromethane, absorbed onto silica gel and then chromatographed using a 5:1 mixture of dichloromethane-ether as eluant. Rotary evaporation of the appropriate fractions left 9.70 g of phenyl (6-chloro-3,4-dihydro-4-methyl-3-oxopyrazin-2-yl)carbamate as a crystalline solid melting at 175°-177° C.

Workup

  1. additionwas added as rapidly as possible
  2. stirringthe reaction mixture was stirred at approximately 0° C. for 3 hours
  3. temperatureto briefly warm to room temperature
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with 10:1 dichloromethane-tetrahydrofuran (5×100 mL)
  6. dry with materialThe combined organic solutions were dried (Na2SO4)
  7. customfurther rotary evaporation
  8. waitleft a tan solid
  9. customabsorbed onto silica gel
  10. customchromatographed
  11. additiona 5:1 mixture of dichloromethane-ether as eluant
  12. customRotary evaporation of the appropriate fractions
  13. waitleft 9.70 g of phenyl (6-chloro-3,4-dihydro-4-methyl-3-oxopyrazin-2-yl)carbamate as a crystalline solid melting at 175°-177° C.

Sources & evidence

ORD record
ord-8714136ec3a548489919741aed04d3cf
Source dataset
uspto-grants-1989_02
Patent number
US04802908

Reaction notes

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