Sodium hydride → 5-Fluoro-2-(1-methyl-3-pyrrolidinyloxy)benzamide

HRID 4797ノート

反応式

HRID 4797 の反応式
[H-].[Na+].[F:3][C:4]1[CH:5]=[CH:6][C:7]([OH:13])=[C:8]([CH:12]=1)[C:9]([NH2:11])=[O:10].CS(O[CH:19]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20]1)(=O)=O>CN(C)C=O>[F:3][C:4]1[CH:5]=[CH:6][C:7]([O:13][CH:19]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20]2)=[C:8]([CH:12]=1)[C:9]([NH2:11])=[O:10]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 137262825-Fluoro-2-hydroxybenzamideHCID 219142741-Methylpyrrolidin-3-yl methanesulfonate

生成物 1

HCID 137262885-Fluoro-2-(1-methyl-3-pyrrolidinyloxy)benzamide収率 42%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
60 °C

実験手順

To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals. m.p. 90°-93° C.

後処理

  1. temperatureThe reaction mixture was then heated to 100° C. for 18 hr
  2. customThe dimethylformamide was removed by rotary evaporation at 70° C.
  3. washwashed with 2×50 ml of 1N sodium hydroxide and 50 ml of water
  4. extractionThe organic phase was extracted with 2×50 ml of 1N hydrochloric acid
  5. washThe combined aqueous extracts were washed with 50 ml of methylene chloride
  6. extractionextracted into 2×50 ml of methylene chloride
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation
  10. customThe residual oil was crystallized from hexane

出典と根拠

ORDレコード
ord-997cc09958b640a1bde80518045ba4ee
出典データセット
uspto-grants-1988_02
特許番号
US04727152

反応ノート

読み込み中…