Hydrochloric Acid → N,N-diethyl-3-(diethylthiocarbamoyloxy)-2-fluoronicotinamide

HRID 52134

反応式

HRID 52134 の反応式
[Li]CCCC.[CH2:6]([N:8]([CH2:19][CH3:20])[C:9]([O:11][C:12]1[C:13]([F:18])=[N:14][CH:15]=[CH:16][CH:17]=1)=[S:10])[CH3:7].[CH2:21]([N:23]([CH2:27][CH3:28])[C:24](Cl)=[O:25])[CH3:22].Cl>C1COCC1.O>[CH2:21]([N:23]([CH2:27][CH3:28])[C:24](=[O:25])[C:12]1([O:11][C:9](=[S:10])[N:8]([CH2:6][CH3:7])[CH2:19][CH3:20])[CH:17]=[CH:16][CH:15]=[N:14][CH:13]1[F:18])[CH3:22]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 6916Diethylcarbamoyl chlorideHCID 199632423-Diethylthiocarbamoyloxy-2-fluoropyridineHCID 178418339Butyllithium

生成物 1

HCID 19963245N,N-diethyl-3-(diethylthiocarbamoyloxy)-2-fluoronicotinamide収率 65%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-10 °C

実験手順

250 ml (400 mmol) of n-BuLi (1.6M in hexane) are added to a solution of 57.9 g (410 mmol) of TMP in 750 ml of THF at -10° C. After the mixture has been stirred for 1 hour at -10° C., a solution of 64 g (280 mmol) of 3-diethylthiocarbamoyloxy-2-fluoropyridine in 200 ml of THF is added dropwise at -78° C. in the course of 30 minutes. After the mixture has been stirred for 1 hour at -78° C., 81.4 g (600 mmol) of diethylcarbamoyl chloride are added in the course of 1 minute, the mixture is stirred at -78° C. for 2 hours and heated to -20° C., 130 ml of 3N HCl are added, and the mixture is diluted with 1 l of water and brought to pH 7. The organic phase is washed 3 times with water. The combined aqueous phases are extracted twice using Et2O, and the combined organic phases are washed twice with water, dried over Na2SO4 and concentrated in vacuo at 60° C.: 116 g of a brown oil. Chromatography (ethyl acetate/hexane 1:1) gives 60 g (65% ) of beige crystals of m.p. 87°-92° C.

後処理

  1. stirringAfter the mixture has been stirred for 1 hour at -78° C.
  2. stirringthe mixture is stirred at -78° C. for 2 hours
  3. temperatureheated to -20° C.
  4. washThe organic phase is washed 3 times with water
  5. extractionThe combined aqueous phases are extracted twice using Et2O
  6. washthe combined organic phases are washed twice with water
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo at 60° C.

出典と根拠

ORDレコード
ord-88ddd8716b694fdaabf8855cf92a9544
出典データセット
uspto-grants-1997_04
特許番号
US05616590

関連ノート

読み込み中…