Lithium Hydroxide → 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acid

HRID 537146Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 537146
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:18]([O:20]CC)=[O:19])[CH:6]=[C:7]2[C:11]=1[N:10]([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1)[N:9]=[CH:8]2.[OH-].[Li+]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:18]([OH:20])=[O:19])[CH:6]=[C:7]2[C:11]=1[N:10]([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1)[N:9]=[CH:8]2

Komponenten

4

Edukt 2

HCID 3939Lithium Hydroxide2×HCID 66920406ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate

Produkt 1

HCID 674914847-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acidAusbeute 92,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate (102 mg, 0.33 mmol) in tetrahydrofuran (2 mL) was added 1 N aqueous lithium hydroxide (0.67 mL, 0.67 mmol). The reaction was stirred at room temperature overnight. LCMS showed the reaction to be incomplete. Additional lithium hydroxide (0.35 mL, 2 M, 0.7 mmol) was added and the reaction was heated to 40° C. for 1 hour. The reaction was then left stirring at room temperature for 70 hours. The tetrahydrofuran was removed in vacuo and the residue was acidified to pH=4 with 1 N aqueous hydrochloric acid. The solution was extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated to give the title compound (84 mg, 91%) as a solid. (M+1-THP) 193.2; 1H NMR (400 MHz, CDCl3, δ): 8.18 (d, J=1.37 Hz, 1H), 8.12 (s, 1H), 7.46 (d, J=1.17 Hz, 1H), 6.26 (dd, J=10.15, 2.54 Hz, 1H), 4.07-4.12 (m, 1H), 4.06 (s, 3H), 3.65-3.81 (m, 1H), 2.54-2.72 (m, 1H), 2.10-2.22 (m, 1H), 2.01-2.10 (m, 1H), 1.71-1.85 (m, 2H), 1.57-1.67 (m, 1H).

Aufarbeitung

  1. customthe reaction
  2. temperaturethe reaction was heated to 40° C. for 1 hour
  3. waitThe reaction was then left
  4. stirringstirring at room temperature for 70 hours
  5. customThe tetrahydrofuran was removed in vacuo
  6. extractionThe solution was extracted with ethyl acetate (3×)
  7. washThe combined organics were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-16a9ea0d4e8d49af9745fc2fadf907c8
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08859773B2

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