Triethylamine → 7-chloro-5-fluoro-3-methylsulfanyl-1H-indole

HRID 23386

反応式

HRID 23386 の反応式
[Cl:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH2:4].ClOC(C)(C)C.CO[CH:18](OC)[CH2:19][S:20][CH3:21].C(N(CC)CC)C>C(Cl)Cl.O>[Cl:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[C:5]2[C:3]=1[NH:4][CH:18]=[C:19]2[S:20][CH3:21]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 75013Benzenamine, 2-chloro-4-fluoro-HCID 521297Tert-Butyl hypochloriteHCID 638113(Methylthio)acetaldehyde dimethyl acetal

生成物 1

HCID 225739857-chloro-5-fluoro-3-methylsulfanyl-1H-indole収率 46.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒4 回

実験手順

Following the procedure described in J.Amer.Chem.Soc. 96 (17), 5495 (1974) 2-chloro-4-fluoroaniline (1.45 g, 10 mmole) was dissolved in methylene chloride (35 ml) and stirred vigorously at −65° C. under nitrogen while freshly prepared t-butyl hypochlorite (1.08 g, 10 mmole) dissolved in 10 ml methylene chloride was added dropwise. Ten minutes after the completion of the addition a solution of 1,1-dimethoxy-2-methylsulfanyl-ethane (1.36 g, 10 mmole) dissolved in 10 ml methylene chloride was added slowly. The reaction mixture was stirred at −65° C. for 1 h after which time, triethyl amine (1.01 g, 10 mmole) dissolved in 10 ml methylene chloride was added and the temperature was allowed to rise to room temperature. Water was added and the organic layer was separated, dried over magnesium sulfate, filtered and evaporated to dryness. The oily residue was taken up in carbon tetrachloride (35 ml) containing triethylamine (2 ml) and refluxed overnight. The solvent was removed and replaced with ether (35 ml) and stirred in a two-phase system with 12 ml of 2N HCl for about 3 h. The ether layer was then separated, washed with bicarbonate solution, dried over magnesium sulfate, filtered and evaporated to dryness. Purification by chromatography on silica gel (1:9 ethyl acetate:hexane) afforded the pure 7-chloro-5-fluoro-3-methylsulfanyl-1H-indole (0.997 g, 46% yield).

後処理

  1. additionwas added dropwise
  2. additionwas added slowly
  3. additionwas added
  4. customto rise to room temperature
  5. customthe organic layer was separated
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness
  9. additioncontaining triethylamine (2 ml)
  10. temperaturerefluxed overnight
  11. customThe solvent was removed
  12. customThe ether layer was then separated
  13. washwashed with bicarbonate solution
  14. dry with materialdried over magnesium sulfate
  15. filtrationfiltered
  16. customevaporated to dryness
  17. customPurification by chromatography on silica gel (1:9 ethyl acetate:hexane)

出典と根拠

ORDレコード
ord-b39f445d51354e3a9a1183d12b6089a0
出典データセット
uspto-grants-2005_02
特許番号
US06852726B2

関連ノート

読み込み中…