Methyl iodide → HCID 89922465, compound

HRID 921879Notes

Reaction equation

HRID 921879 reaction equation
[O:1]=[C:2]1[CH:7]2[CH2:8][N:9]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])[CH2:10][CH2:11][N:6]2[CH2:5][CH2:4][NH:3]1.[H-].[Na+].I[CH3:25]>C1COCC1>[CH3:25][N:3]1[CH2:4][CH2:5][N:6]2[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])[CH2:8][CH:7]2[C:2]1=[O:1]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 89922723HCID 89922723, compound

Product 1

HCID 89922465HCID 89922465, compoundYield 71.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (+/−)-benzyl 9-oxohexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate (160 mg, 0.553 mmol) in THF (5 mL) at 0° C. was added sodium hydride (24.33 mg, 0.608 mmol). The ice bath was removed and stirred for 10 min; saw bubbling but some NaH solid still remained. Then iodomethane (0.038 mL, 0.608 mmol) was added and after stirring for 10 min at room temperature, most NaIl solid was dissolved. After another 30 min, LC-MS indicated completion. It was quenched with water and diluted with EtOAc. After separating the layers, the aqueous layer was further extracted with EtOAc. The combined organic extracts were washed with water, brine, dried over MgSO4, filtered and concentrated. Purification via flash chromatography (0-5% MeOH in DCM, 12 g) gave (+/−)-benzyl 8-methyl-9-oxohexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate (120 mg) as a light yellow oil.

Workup

  1. customThe ice bath was removed
  2. customsaw bubbling
  3. stirringafter stirring for 10 min at room temperature
  4. dissolutionmost NaIl solid was dissolved
  5. waitAfter another 30 min
  6. customIt was quenched with water
  7. additiondiluted with EtOAc
  8. customAfter separating the layers
  9. extractionthe aqueous layer was further extracted with EtOAc
  10. washThe combined organic extracts were washed with water, brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customPurification via flash chromatography (0-5% MeOH in DCM, 12 g)

Sources & evidence

ORD record
ord-a8870599133243b688426edfce63eae4
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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