Hydrogen Peroxide → tert-butyl 8-carbamoyl-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 589863Notes

Reaction equation

HRID 589863 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][N:6]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:7]=12)#[N:2].[OH-].[Na+].OO.S([O-])([O-])(=[O:25])=S.[Na+].[Na+]>CO.O>[C:1]([C:3]1[CH:4]=[CH:5][N:6]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:7]=12)(=[O:25])[NH2:2]

Participants

7

Reactant 4

HCID 784Hydrogen Peroxide2×HCID 14798Sodium HydroxideHCID 24477Sodium ThiosulfateHCID 86680813tert-butyl 8-cyano-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

Product 1

HCID 66585088tert-butyl 8-carbamoyl-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylateYield 73.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 26.7 g (108 mmol) of tert-butyl 8-cyano-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in 490 ml of methanol are added 80 ml (864 mmol) of concentrated aqueous 32% sodium hydroxide and 4.0 g (41 mmol) of aqueous 35% hydrogen peroxide solution. The reaction medium is heated at 55° C. for 2 hours. 4 times 4.0 g (41 mmol) of aqueous 35% hydrogen peroxide solution are then added every 2 hours and heating is then continued at 55° C. for 18 hours. The medium is then treated with an aqueous solution of 30 g (190 mmol) of sodium thiosulfate in 250 ml of water and the reaction mixture is stirred for 1 hour and then partially concentrated under reduced pressure. The product is extracted with 350 ml and then twice 100 ml of dichloromethane, and the organic phases are combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is dissolved in a mixture of dichloromethane and ethyl acetate and then precipitated by slow concentration to give 21.1 g of tert-butyl 8-carbamoyl-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in the form of a white solid after drying in an oven at 60° C. under reduced pressure.

Workup

  1. temperatureheating
  2. concentrationpartially concentrated under reduced pressure
  3. extractionThe product is extracted with 350 ml
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue is dissolved in a mixture of dichloromethane and ethyl acetate
  8. customprecipitated by slow concentration

Sources & evidence

ORD record
ord-abe632f9f606460f8a125e1069a08dfb
Source dataset
uspto-grants-2016_01
Patent number
US09233965B2

Reaction notes

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