Methyl iodide → Tert-butyl(6-bromo-3-methoxypyridin-2-yl)(methyl)carbamate

HRID 1772887Notes

Reaction equation

HRID 1772887 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:19])[NH:9][C:10]1[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([Br:18])[N:11]=1)([CH3:6])([CH3:5])[CH3:4].I[CH3:21].[NH4+].[Cl-]>CC1OCCC1.O>[C:3]([O:7][C:8](=[O:19])[N:9]([C:10]1[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([Br:18])[N:11]=1)[CH3:21])([CH3:6])([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 6328Methyl iodide2×HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 131734688Tert-butyl(6-bromo-3-methoxypyridin-2-yl)carbamate

Product 1

HCID 118685223Tert-butyl(6-bromo-3-methoxypyridin-2-yl)(methyl)carbamateYield 90.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 73012-MethyltetrahydrofuranSolvent2×

Procedure

NaH (60% in oil, 1.90 g, 47.5 mmol) was added to cooled (5° C.) anhydrous 2-MeTHF (120 mL) under argon, followed by a solution of tert-butyl(6-bromo-3-methoxypyridin-2-yl)carbamate (4.80 g, 15.8 mmol) in anhydrous 2-MeTHF (40 mL) slowly, maintaining the reaction temperature below 15° C. Once the addition was complete the reaction was stirred for 15 min prior to addition of iodomethane (2.76 mL, 44.3 mmol). After stirring at rt for 21 h, further iodomethane (2.76 mL, 44.3 mmol) was added and the reaction mixture stirred at rt for 1 d. After cooling to 5° C. saturated aqueous NH4Cl and H2O (1:1, 160 mL) was added with caution. The mixture was stirred at rt for 15 min, the phases were separated and the aqueous phase extracted with EtOAc (2×200 mL). The combined organic phases were washed with brine, dried (Na2SO4) and concentrated in vacuo before purification by gradient flash chromatography, eluting with 5-25% EtOAc in heptane yielded tert-butyl(6-bromo-3-methoxypyridin-2-yl)(methyl)carbamate (4.52 g, 14.3 mmol) as a colourless oil.

Workup

  1. temperaturemaintaining the reaction temperature below 15° C
  2. additionOnce the addition
  3. stirringAfter stirring at rt for 21 h
  4. stirringthe reaction mixture stirred at rt for 1 d
  5. additionwas added with caution
  6. stirringThe mixture was stirred at rt for 15 min
  7. customthe phases were separated
  8. extractionthe aqueous phase extracted with EtOAc (2×200 mL)
  9. washThe combined organic phases were washed with brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo before purification by gradient flash chromatography
  12. washeluting with 5-25% EtOAc in heptane

Sources & evidence

ORD record
ord-e6081af02e7b4c629a8f109793c0c723
Source dataset
uspto-grants-2016_02
Patent number
US09249160B2

Reaction notes

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