2,2,6,6-Tetramethylpiperidine → 2,4-Difluoro-5-[hydroxy(1,3-thiazol-2-yl)methyl]-3-methylbenzoic acid

HRID 245383ノート

反応式

HRID 245383 の反応式
[Li]CCCC.CC1(C)CCCC(C)(C)N1.[F:16][C:17]1[C:25]([CH3:26])=[C:24]([F:27])[CH:23]=[CH:22][C:18]=1[C:19]([OH:21])=[O:20].[S:28]1[CH:32]=[CH:31][N:30]=[C:29]1[CH:33]=[O:34]>C1COCC1>[F:16][C:17]1[C:25]([CH3:26])=[C:24]([F:27])[C:23]([CH:33]([OH:34])[C:29]2[S:28][CH:32]=[CH:31][N:30]=2)=[CH:22][C:18]=1[C:19]([OH:21])=[O:20]

参加物

6

反応物 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 27349031,3-Thiazole-2-carbaldehydeHCID 139868372,4-Difluoro-3-methylbenzoic acid2 回HCID 178418339Butyllithium

生成物 1

HCID 866580582,4-Difluoro-5-[hydroxy(1,3-thiazol-2-yl)methyl]-3-methylbenzoic acid

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-78 °C

実験手順

A solution of 1.9 M n-BuLi (3.8 ml, 7.2 mmol) in hexanes was added at −30° C. to a stirred solution of 2,2,6,6-tetramethylpiperidine (1.2 g, 9.0 mmol) in THF and the mixture was stirred for an hour at the same temperature. After cooling to −78° C., a solution of 2,4-difluoro-3-methylbenzoic acid (Intermediate 46, 0.5 g, 3.0 mmol) in THF was added slowly at and the mixture was stirred for another 2 h at the same temperature. To this mixture, a solution of thiazole-2-carboxaldehyde (0.8 g, 7.2 mmol) in THF was added dropwise over a period of 10 mins and the mixture was brought to the room temperature. The reaction mixture was quenched with 1.5N hydrochloric acid and the organic layer was separated, the aqueous layer was extracted with ethyl acetate (3×10 mL) and the combined organic layer was dried over sodium sulfate. Removal of solvent afforded the title compound as colorless product. Yield: 0.42 g (51%).

後処理

  1. stirringwas stirred for another 2 h at the same temperature
  2. customwas brought to the room temperature
  3. customThe reaction mixture was quenched with 1.5N hydrochloric acid
  4. customthe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×10 mL)
  6. dry with materialthe combined organic layer was dried over sodium sulfate
  7. customRemoval of solvent

出典と根拠

ORDレコード
ord-ada357377476488f82fe9f2fe8bc59cb
出典データセット
uspto-grants-2014_02
特許番号
US08658641B2

反応ノート

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