Water → 5-Chloromethyl-1-(4-fluorophenyl)-1h-indole

HRID 394586ノート

反応式

HRID 394586 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH2:17]O)=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.CS([Cl:30])(=O)=O.O>ClCCl>[Cl:30][CH2:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[CH:9]=[CH:10]2

参加物

6

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 699825031-(4-Fluorophenyl)-5-hydoxymethyl-1H-indole

生成物 1

HCID 181772135-Chloromethyl-1-(4-fluorophenyl)-1h-indole収率 118.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
2.5 °C

実験手順

To a solution of 1-(4-fluorophenyl)-5-hydoxymethyl-1H-indole (10a) (21.5 g) and triethyl amine (21.5 mL) in dichloromethane a solution of methanesulfonyl chloride (15.3 g) in dichloromethane was added at 0-5° C. After stirring at 0-5° C. for 2 h, water (600 mL) was added the phases were separated and the aqueous phase was extracted with dichloromethane (500 mL). The combined organic phases were dried (MgSO4) and the solvents evaporated affording 5-chloromethyl-1-(4-fluorophenyl)-1H-indole as an oil (27.5 g). A solution of the crude chloromethyl derivative in dimethyl sulfoxide was added to a solution of sodium cyanide in dimethyl sulfoxide at 80° C. After heating of the reaction mixture at 80° C. for further 40 minutes, the reaction mixture was cooled to room temperature and water (900 ml) was added. The resulting mixture was extracted with diethyl ether (2×1.5 L) and the combined organic phases were washed with brine (2×1.5 L). Drying of the combined organic phases (Na2SO4), evaporation of the solvents and purification by column chromatography on silica gel (ethyl acetate/heptane 1:3) afforded pure 5-cyanomethyl-1-(4-fluorophenyl)-1H-indole as an oil (8.2 g): 1H NMR (CDCl3) δ 3.80 (s, 2H), 6.60 (d, 1H), 7.05-7.25 (m, 3H), 7.25 (d, 1H), 7.35-7.45 (m, 3H), 7.60 (broad s, 1H).

後処理

  1. customwere separated
  2. extractionthe aqueous phase was extracted with dichloromethane (500 mL)
  3. dry with materialThe combined organic phases were dried (MgSO4)
  4. customthe solvents evaporated

出典と根拠

ORDレコード
ord-c96df6953c0848ebbc9d7c62c2cb3e13
出典データセット
uspto-grants-2003_08
特許番号
US06602889B1

反応ノート

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