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Dimethyl-1,3-thiazole-5-carboxylic acid → 2-{2-[5-(4-fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-2-hydroxy-ethyl}-4-methyl-thiazole-5-carboxylic acid

HRID 2365229
ノート
印刷プレビュー

反応式

HRID 2365229 の反応式
[CH3:1][C:2]1[S:3][C:4]([C:8]([OH:10])=[O:9])=[C:5]([CH3:7])[N:6]=1.[Li]CCCC.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:27]=[N:26][N:25]([CH3:28])[C:24]=2[CH:29]=[O:30])=[CH:19][CH:18]=1>C1COCC1>[F:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[N:27]=[N:26][N:25]([CH3:28])[C:24]=2[CH:29]([OH:30])[CH2:1][C:2]2[S:3][C:4]([C:8]([OH:10])=[O:9])=[C:5]([CH3:7])[N:6]=2)=[CH:21][CH:22]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 736488Dimethyl-1,3-thiazole-5-carboxylic acidHCID 866647645-(4-Fluoro-phenyl)-3-methyl-3H-[1,2,3]-triazole-4-carbaldehydeHCID 178418339Butyllithium

生成物 1

HCID 674976492-{2-[5-(4-fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-2-hydroxy-ethyl}-4-methyl-thiazole-5-carboxylic acid収率 77%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran
溶媒
2 回

反応条件

温度
-75 °C

実験手順

To a suspension of 2,4-dimethylthiazole-5-carboxylic acid (236 mg, 1.5 mmol) in THF (12 mL) was added dropwise n-BuLi (1.6 M in hexanes, 1.88 mL, 3.0 mmol) under Ar at −75° C. The brown suspension was stirred at −75° C. for 2 h and then a solution of 5-(4-fluoro-phenyl)-3-methyl-3H-[1,2,3]triazole-4-carbaldehyde (308 mg, 1.50 mmol) in THF (4.5 mL) was added at −75° C. and the brown suspension was stirred at −75° C. for 2 h. The mixture was then quenched with an aqueous solution of citric acid (5%, 15 mL), allowed to warm to room temperature. The mixture was then poured into saturated ammonium chloride solution and extracted with ethyl acetate and the combined organic extracts washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, 0 to 30% methanol in dichloromethane) afforded 2-{2-[5-(4-fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-2-hydroxy-ethyl}-4-methyl-thiazole-5-carboxylic acid (417 mg, 77%) as a yellow foam. The acid was then dissolved in methanol (4 mL) and diethylether (2 mL) and trimethylsilyldiazomethane (2M in diethylether, 5×0.38 mL, 3.75 mmol) added dropwise. The reaction was quenched with a few drops of AcOH and evaporated. To the brown oil was added sodium hydroxide (1 N, 20 mL) and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated. Purification by chromatography (silica, 0 to 30% methanol in dichloromethane) afforded the title compound (214 mg, 38%) as a light brown foam.

後処理

  1. stirringthe brown suspension was stirred at −75° C. for 2 h
  2. customThe mixture was then quenched with an aqueous solution of citric acid (5%, 15 mL)
  3. temperatureto warm to room temperature
  4. additionThe mixture was then poured into saturated ammonium chloride solution
  5. extractionextracted with ethyl acetate
  6. washthe combined organic extracts washed with brine
  7. dry with materialdried over sodium sulphate
  8. filtrationfiltered
  9. customevaporated
  10. customPurification by chromatography (silica, 0 to 30% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-c39ed4d8915846e8b516dfe8357845e9
出典データセット
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08697696B2

反応ノート

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