Formaldehyde → 4-Chloro-2-(2-hydroxy-ethyl)-N-(tetrahydro-pyran-4-yl)-benzamide

HRID 540359ノート

反応式

HRID 540359 の反応式
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([NH:8][CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[O:7])=[C:4]([CH3:17])[CH:3]=1.C(NC(C)C)(C)C.[Li]C(CC)C.C=O.[C:32](=O)=[O:33].CC(C)=O>C1COCC1.C(Cl)Cl.CO>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([NH:8][CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[O:7])=[C:4]([CH2:17][CH2:32][OH:33])[CH:3]=1

参加物

9

反応物 5

HCID 712FormaldehydeHCID 7912DiisopropylamineHCID 18522661Acetone cardiceHCID 674690494-Chloro-2-methyl-N-(tetrahydro-pyran-4-yl)-benzamideHCID 178418400CID 53628100

生成物 1

HCID 674660274-Chloro-2-(2-hydroxy-ethyl)-N-(tetrahydro-pyran-4-yl)-benzamide収率 54%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

4-Chloro-2-methyl-N-(tetrahydro-pyran-4-yl)-benzamide (2.09 g, 8.24 mmol) and diisopropylamine (0.15 equiv. 1.24 mmol, 125 mg.) were dissolved in anhydrous THF (100 mL). The solution was cooled to −78° C. When cooled at −78° C. it becomes a white suspension. To this solution was added sec-BuLi (1.4 M, in cyclohexane; 13 mL, 18.5 mmol, 2.25 equiv.), the reaction mixture turns into orange color, stirred for 5 min, and then submerged into ice-water bath (0° C.) for 15 min, the reaction becomes a clear orange solution, re-cooled to −78° C. Powdered formaldehyde (1.48 g, 49.44 mmol, 36 equiv.) was added. The dry ice-acetone bath was replaced with an ice-water and stirring was continued for 30 min. The red-brown color faded away to a light yellow color. The reaction was quenched with water, diluted with EtOAc. The two layers were separated and the aqueous was extracted with EtOAc (2×10 mL). The combined EtOAc solution was washed with brine (20 mL). Then, the EtOAc solution was dried over anhydrous granular K2CO3, filtered, and concentrated in vacuo. The crude product showed 2 peaks at 2.348 min, MS 284; 2.150 min, MS 254 at 2.808 (SM). The compound was purified on a 70-g silica gel column eluted with 1-5 min. 0-2.5% MeOH in DCM to obtain 1.25 g (54% yield) of the title compound as a white solid.

後処理

  1. temperatureWhen cooled at −78° C. it
  2. customsubmerged into ice-water bath
  3. wait(0° C.) for 15 min
  4. temperaturere-cooled to −78° C
  5. stirringstirring
  6. waitwas continued for 30 min
  7. customThe reaction was quenched with water
  8. additiondiluted with EtOAc
  9. customThe two layers were separated
  10. extractionthe aqueous was extracted with EtOAc (2×10 mL)
  11. washThe combined EtOAc solution was washed with brine (20 mL)
  12. dry with materialThen, the EtOAc solution was dried over anhydrous granular K2CO3
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customat 2.348 min
  16. custom2.150 min, MS 254
  17. customThe compound was purified on a 70-g silica gel column
  18. washeluted with 1-5 min

出典と根拠

ORDレコード
ord-d10006f22e9c44179f8cd0619a4a022e
出典データセット
uspto-grants-2014_10
特許番号
US08871788B2

反応ノート

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