Methyl iodide → Tert-butyl (6-chloro-4-iodopyridin-3-yl)(methyl)carbamate

HRID 1951654Notes

Reaction equation

HRID 1951654 reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:9]=[N:10][C:11]([Cl:15])=[CH:12][C:13]=1[I:14])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:20]>CN(C=O)C>[C:1]([O:5][C:6](=[O:16])[N:7]([C:8]1[CH:9]=[N:10][C:11]([Cl:15])=[CH:12][C:13]=1[I:14])[CH3:20])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 53415320tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamate2×

Product 1

HCID 57443399Tert-butyl (6-chloro-4-iodopyridin-3-yl)(methyl)carbamateYield 102%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1.00 g (2.82 mmol) (6-chloro-4-iodo-pyridin-3-yl)-carbamic acid tert-butyl ester in 10 ml DMF were added 0.12 g (3.1 mmol) sodium hydride (60% in mineral oil) at −10° C. (The preparation of (6-chloro-4-iodo-pyridin-3-yl)-carbamic acid tert-butyl ester has been described in US 2002/0022624 A1.) The reaction mixture was allowed to warm to room temperature. After 1 h, the mixture was cooled back to −10° C., and 0.44 ml (7.1 mmol) iodomethane were added during 5 min. The reaction mixture was allowed to warm to room temperature. After 2.5 h at room temperature, the reaction was quenched by addition of 10 ml of a saturated aqueous solution of NaHCO3 and the mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, hexanes/ethyl acetate=4:1) to give 1.06 g (100%) of the title compound as a colorless oil.

Workup

  1. temperaturethe mixture was cooled back to −10° C.
  2. temperatureto warm to room temperature
  3. waitAfter 2.5 h at room temperature
  4. customthe reaction was quenched by addition of 10 ml of a saturated aqueous solution of NaHCO3
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (silica gel, hexanes/ethyl acetate=4:1)

Sources & evidence

ORD record
ord-d3af0ba1f270420a8f5a336c99e00406
Source dataset
uspto-grants-2013_03
Patent number
US08404708B2

Reaction notes

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