2,6-Lutidine → 3-Amino-5-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-4-chlorobenzonitrile

HRID 1430799ノート

反応式

HRID 1430799 の反応式
[Si:1]([O:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]2[C:16]([Cl:31])=[C:17]([NH:23]C(=O)OC(C)(C)C)[CH:18]=[C:19]([C:21]#[N:22])[CH:20]=2)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O>ClCCl>[NH2:23][C:17]1[CH:18]=[C:19]([CH:20]=[C:15]([N:12]2[CH2:11][CH2:10][CH:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3])[CH2:14][CH2:13]2)[C:16]=1[Cl:31])[C:21]#[N:22]

参加物

5

反応物 3

HCID 79372,6-LutidineHCID 65367Trimethylsilyl triflateHCID 86708480Tert-butyl (3-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate

生成物 1

HCID 867084823-Amino-5-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-4-chlorobenzonitrile収率 73.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

(I13B): To a round bottom flask charged with tert-butyl (3-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate (I13A) (3.27 g, 7.02 mmol) in dichloromethane (35.1 ml) and cooled to 0° C. was added 2,6-lutidine (2.451 ml, 21.05 mmol). Trimethylsilyl trifluoromethanesulfonate (3.80 ml, 21.05 mmol) was added dropwise over 5 min. After 1 h, the reaction mixture was quenched by the addition of saturated aqueous sodium bicarbonate and dichloromethane. The mixture was transferred to a separatory funnel and the aqueous layer was extracted with dichloromethane (3×). The combined organics were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by column chromatography on the Isco system (120 g, 0-50% EtOAc/CH2Cl2). 3-amino-5-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-4-chlorobenzonitrile (I13B) (1.892 g) was isolated as a sticky yellow oil.

後処理

  1. customthe reaction mixture was quenched by the addition of saturated aqueous sodium bicarbonate and dichloromethane
  2. customThe mixture was transferred to a separatory funnel
  3. extractionthe aqueous layer was extracted with dichloromethane (3×)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by column chromatography on the Isco system (120 g, 0-50% EtOAc/CH2Cl2)

出典と根拠

ORDレコード
ord-d7ea757e20ab44da92a2f9b3fb3b7c0c
出典データセット
uspto-grants-2015_01
特許番号
US08940736B2

反応ノート

読み込み中…