Hydrochloric Acid → 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoic acid

HRID 218140Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 218140
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:18]([CH3:23])[C:19]([O:21]C)=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.Cl>[OH-].[Na+].CO.CS(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH:18]([CH3:23])[C:19]([OH:21])=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 67005256methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoate

Produkt 1

HCID 592510523-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoic acidAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 86640187NaOH MeOH DMSOLösungsmittel

Versuchsvorschrift

(a)(b) To a solution of (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (800 mg, 2.5 mmol) and (1-methoxyprop-1-enyloxy)trimethylsilane (1 mL, 6.25 mmol) in 30 mL of dry DCM was added TiCl4 (2.5 mL of 1.0 M DCM solution, 2.5 mmol) and then stirred 1 h. The reaction was quenched with MeOH, poured into aqueous sodium bicarbonate and extracted 2× EtOAc. The organic layers were dried over MgSO4, filtered, concentrated to give methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoat. Crude methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoate was heated to 100 C overnight in a mixture of 2 M NaOH/MeOH/DMSO (1:1:1). The next day, the reaction was cooled, acidified to pH 5 with HCl and extracted 2× EtOAc. The organic layers were washed with water×2, dried over MgSO4, filtered, concentrated in vacuo, and purified by HPLC to give 770 mg (82% yield, 2 steps) of acid 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoic acid which could be separated into its four isomers by chiral HPLC. MS found: (M+H)+=375.

Aufarbeitung

  1. temperatureThe next day, the reaction was cooled
  2. extractionextracted 2× EtOAc
  3. washThe organic layers were washed with water×2
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by HPLC

Quellen und Nachweise

ORD-Eintrag
ord-b5ab9427fa5e45b18a5b097997700e2a
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08198311B2

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