Methyl iodide → HCID 71201955, compound

HRID 1908684Notes

Reaction equation

HRID 1908684 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]1[N:11]=[CH:10][C:9]([C@@H:12]([NH:15][C:16]([C@H:18]2[CH2:20][C@@H:19]2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:17])[CH2:13][OH:14])=[CH:8][CH:7]=1)[CH3:4].[CH3:27]I>CN(C=O)C.[Cl-].[Na+].O>[CH2:3]([O:5][C:6]1[N:11]=[CH:10][C:9]([C@@H:12]([NH:15][C:16]([C@H:18]2[CH2:20][C@@H:19]2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:17])[CH2:13][O:14][CH3:27])=[CH:8][CH:7]=1)[CH3:4]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydride2×HCID 71201944HCID 71201944, compound2×

Product 1

HCID 71201955HCID 71201955, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 57417360Sodium chloride; waterSolvent

Procedure

NaH (60% suspension in mineral oil) (2.06 g, 51.5 mmol) was suspended in DMF and the reaction vessel was cooled in an ice bath. (1S,2S)-2-Phenyl-cyclopropanecarboxylic acid [(R)-1-(6-ethoxy-pyridin-3-yl)-2-hydroxy-ethyl]-amide (Compound 33) (15 g, 46 mmol) was dissolved in DMF (50 ml) and added drop wise to the sodium hydride suspension at 5-8 C over 20 minutes. The solution was stirred 30 minutes. Methyl iodide (3.30 ml, 53.0 mmol) dissolved in DMF (25 ml) was added drop wise at 5-12 C over 10 minutes and the mixture was stirred at 7-8 C for 30 minutes. The mixture was added to a brine solution and extracted with EtOAc. The organic layer was washed with more brine, dried (MgSO4) filtered and the solvent was evaporated off. The crude product was purified by silica gel chromatography (eluent EtOAc in heptanes 4:1). The fractions that contained the product was collected and the solvent was removed in vac. The residue was redissolved in THF (50 ml) EtOAc (100 ml) and heptanes (25 ml). The mixture was concentrated until 40 ml remained and cooled in ice. A white solid precipitated and was collected by filtration. Yield: 6.75 g (43%) of Compound 46. LC-MS (m/z) 341.2 (MH+), tR=0.64 min (method B).

Workup

  1. temperaturethe reaction vessel was cooled in an ice bath
  2. additionwas added drop wise at 5-12 C over 10 minutes
  3. stirringthe mixture was stirred at 7-8 C for 30 minutes
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with more brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated off
  9. customThe crude product was purified by silica gel chromatography (eluent EtOAc in heptanes 4:1)
  10. customwas collected
  11. customthe solvent was removed in vac
  12. dissolutionThe residue was redissolved in THF (50 ml) EtOAc (100 ml)
  13. concentrationThe mixture was concentrated until 40 ml
  14. temperaturecooled in ice
  15. customA white solid precipitated
  16. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-00d5b8421f2f4b6c9248262e0728ec67
Source dataset
uspto-grants-2013_12
Patent number
US08598213B2

Reaction notes

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