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

HRID 711069노트

반응식

HRID 711069 반응식
[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

참가 물질

4

반응물 2

HCID 3939Lithium Hydroxide2회HCID 66920406ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate

생성물 1

HCID 674914847-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acid수율 92.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a5bb5de2a5df45fb9f30c77eed557254
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181252B2

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