氢氧化锂 → 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acid

HRID 711069笔记

反应方程式

HRID 711069 反应方程式
[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

参与物

4

反应物 2

HCID 3939氢氧化锂2 次HCID 66920406ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate

产物 1

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

试剂、催化剂与溶剂 1

HCID 8028四氢呋喃溶剂

实验过程

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).

后处理

  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

来源与证据

ORD记录
ord-a5bb5de2a5df45fb9f30c77eed557254
来源数据集
uspto-grants-2015_11
专利号
US09181252B2

反应笔记

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