Methyl iodide → HCID 117843295, compound

HRID 2209308Notes

Reaction equation

HRID 2209308 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[NH:9][C:10]([CH:12]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1)=[O:11].[H-].[Na+].I[CH3:26]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[N:9]([CH3:26])[C:10]([CH:12]1[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15]1)=[O:11]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 117843009HCID 117843009, compound

Product 1

HCID 117843295HCID 117843295, compoundYield 94.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl 3-((2-bromo-5-chlorophenyl)carbamoyl)azetidine-1-carboxylate 7.56 (400 mg, 1.03 mmol) in THF (3 mL) was cooled 0° C. Sodium hydride (60%, 63 mg, 1.58 mmol) was added and mixture stirred at 0° C. for 15 minutes. Iodomethane (0.45 mL, 7.23 mmol) was then added dropwise and the mixture was warmed to rt and stirred overnight. Reaction mixture was quenched with water and taken up in EtOAc. Layers were separated, and aqueous was extracted with ethyl acetate. Combined organics were washed with brine, dried (Na2SO4), filtered, concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-35% ethyl acetate/hexanes) to yield tert-butyl 3-((2-bromo-5-chlorophenyl)(methyl)carbamoyl)azetidine-1-carboxylate 7.57 (393 mg). LCMS-ESI+ (m/z): [M+H]+ calcd for C16H21BrClN2O3: 402.03; found: 402.75.

Workup

  1. temperaturethe mixture was warmed to rt
  2. stirringstirred overnight
  3. customReaction mixture
  4. customwas quenched with water
  5. customLayers were separated
  6. extractionaqueous was extracted with ethyl acetate
  7. washCombined organics were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue was purified via silica gel column chromatography (0-35% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a20e844de3394c8296fd3c05b340f735
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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