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

HRID 887714ノート

反応式

HRID 887714 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒

反応条件

温度
-78 °C

実験手順

(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

後処理

  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)

出典と根拠

ORDレコード
ord-cab9186bbf7f48219b2814aa80532da4
出典データセット
uspto-grants-2012_08
特許番号
US08247431B2

反応ノート

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