Lithium Hydroxide → 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid

HRID 216549

Reaktionsgleichung

Reaktionsgleichung von HRID 216549
C[O:2][C:3]([C:5]1[C:20]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:23]=2[Cl:29])=[C:19]([F:30])[C:8]2[N:9]=[CH:10][N:11]([CH2:12][CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)[C:7]=2[CH:6]=1)=[O:4].O1CCCC1.O.[Li+].[OH-]>O.Cl.C(OCC)(=O)C.O1CCCC1>[Br:28][C:25]1[CH:26]=[CH:27][C:22]([NH:21][C:20]2[C:5]([C:3]([OH:4])=[O:2])=[CH:6][C:7]3[N:11]([CH2:12][CH:13]4[CH2:18][CH2:17][CH2:16][CH2:15][O:14]4)[CH:10]=[N:9][C:8]=3[C:19]=2[F:30])=[C:23]([Cl:29])[CH:24]=1

Komponenten

7

Edukt 3

HCID 3939Lithium HydroxideHCID 21881883Oxolane--water (1/1)HCID 688190776-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

Produkt 1

HCID 211141606-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acidAusbeute 100 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 313Hydrochloric AcidLösungsmittelHCID 962WaterLösungsmittel2×HCID 21939870Tetrahydrofuran ethyl acetateLösungsmittel

Versuchsvorschrift

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester 11q is suspended in 4:1 tetrahydrofuran/water (2.5 mL) and aqueous 1 M LiOH is added (2.5 mL). After stirring at room temperature for 16 hours, the reaction mixture is homogeneous and the reaction is complete. The reaction mixture is cooled to 0° C., diluted with water and aqueous 2 M HCl is added dropwise until the pH of the solution is 1-2, at which time it turns to a suspension. The reaction mixture is poured into a separatory funnel and diluted with ethyl acetate/tetrahydrofuran and water and the layers separated. The aqueous layer is extracted with ethyl acetate. The combined organic layers are washed with brine, dried (Na2SO4) and concentrated under reduced pressure to yield 0.11 g (100%) of the pure desired product as a white solid. MS ESI (+) m/z 482, 484 (M+, Br pattern) detected.

Aufarbeitung

  1. additionis added (2.5 mL)
  2. temperatureThe reaction mixture is cooled to 0° C.
  3. additionis added dropwise until the pH of the solution
  4. additionThe reaction mixture is poured into a separatory funnel
  5. customthe layers separated
  6. extractionThe aqueous layer is extracted with ethyl acetate
  7. washThe combined organic layers are washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-55ae919671594e7995702dbf17180d36
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193230B2

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