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

HRID 245383Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245383
[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]

Komponenten

6

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-ada357377476488f82fe9f2fe8bc59cb
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658641B2

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