4-(Boc-amino)pyridine → tert-butyl N-[3-(2-hydroxyethyl)pyridin-4-yl]carbamate

HRID 272701

反応式

HRID 272701 の反応式
[C:1]([O:5][C:6](=[O:14])[NH:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[Li]C(C)(C)C.Br[CH:21]([OH:23])[CH3:22].[Li]CCCC>C1COCC1>[C:1]([O:5][C:6](=[O:14])[NH:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[CH2:22][CH2:21][OH:23])([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 99902104-(Boc-amino)pyridineHCID 14202443Ethanol, 1-bromo-HCID 178418306HCID 178418306、化合物HCID 178418339Butyllithium

生成物 1

HCID 11031933tert-butyl N-[3-(2-hydroxyethyl)pyridin-4-yl]carbamate収率 19.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

Solution A was prepared by combining pyridin-4-yl-carbamic acid tert-butyl ester (388 mg, 2 mmol) in THF (5 mL) and cooling to −78° C. t-BuLi (2.8 mL, 1.7M solution in pentane) was added dropwise. Once the addition was complete, the solution was stirred at −78° C. for 15 minutes, then warmed to −15° C. and stirred for 90 minutes. In a separate flask, solution B was prepared by combining bromoethanol (0.21 mL, 3 mmol) in THF (5 mL) and cooling to −78° C. n-BuLi (1.44 mL, 2.5M solution in hexanes) was added dropwise. Once the addition was complete, the solution was stirred at −78° C. for 10 minutes. Solution A was recooled to −78° C., and solution B was added to solution A via cannula. Stirred with warming to room temperature for 2 hours. The reaction was recooled, and quenched with water. Partitioned between CH2Cl2 and water. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 100% ethyl acetate to provide 91 mg (19%) of [3-(2-hydroxy-ethyl)-pyridin-4-yl]-carbamic acid tert-butyl ester.

後処理

  1. customSolution A was prepared
  2. additionwas added dropwise
  3. additionOnce the addition
  4. temperaturewarmed to −15° C.
  5. stirringstirred for 90 minutes
  6. additionwas added dropwise
  7. additionOnce the addition
  8. stirringthe solution was stirred at −78° C. for 10 minutes
  9. customwas recooled to −78° C.
  10. stirringStirred
  11. temperaturewith warming to room temperature for 2 hours
  12. customquenched with water
  13. customPartitioned between CH2Cl2 and water
  14. washThe organic layer was washed with brine
  15. dry with materialdried (MgSO4)
  16. filtrationfiltered
  17. concentrationconcentrated under vacuum
  18. customThe residue was purified by flash column chromatography on silica gel with 100% ethyl acetate

出典と根拠

ORDレコード
ord-35cea2680c134738a9e99f915b2e684b
出典データセット
uspto-grants-2008_11
特許番号
US07456169B2

関連ノート

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