Methyl iodide → Tert-butyl (6-chloro-4-methylpyridin-3-YL)carbamate

HRID 887714Notes

Reaction equation

HRID 887714 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:9]=[N:10][C:11]([Cl:14])=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:16]([Li])CCC.CI>C(OCC)C>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:9]=[N:10][C:11]([Cl:14])=[CH:12][C:13]=1[CH3:16])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 7330593(6-Chloro-pyridin-3-yl)-carbamic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 58599548Tert-butyl (6-chloro-4-methylpyridin-3-YL)carbamate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

(6-Chloro-pyridin-3-yl)-carbamic acid tert-butyl ester (14.11 g) was dissolved in dry diethyl ether (310 mL), N,N,N′,N′-tetramethyl-ethylene-1,2-diamine (23.1 mL) was added. The solution was cooled to −78° C., n-butyl lithium (97 mL, 1.59 M in hexane) was added, the cool bath replaced by an ice/sodium chloride cool bath and the suspension was stirred for 2 h at −10° C. The suspension was cooled again to −78° C. and methyl iodide (5.8 mL) was added slowly. The cool bath was removed and the reaction was quenched after 1 h by addition of water. Ethyl acetate was added and the mixture was neutralized by addition of 2 M hydrochloric acid. The layers were separated and the aqueous layer was extracted 2× with ethyl acetate, the combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate 5:1, Rf=0.10) to afford 4.24 g of the title compound of the formula

Workup

  1. temperaturecool bath
  2. temperatureThe suspension was cooled again to −78° C.
  3. customThe cool bath was removed
  4. customthe reaction was quenched after 1 h by addition of water
  5. additionEthyl acetate was added
  6. additionthe mixture was neutralized by addition of 2 M hydrochloric acid
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted 2× with ethyl acetate
  9. washthe combined organic layer was washed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuum
  12. customThe residue was purified by column chromatography (silica 60, hexane/ethyl acetate 5:1, Rf=0.10)

Sources & evidence

ORD record
ord-cab9186bbf7f48219b2814aa80532da4
Source dataset
uspto-grants-2012_08
Patent number
US08247431B2

Reaction notes

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