Potassium Hydroxide → tert-butyl 5-(difluoromethoxy)-3-iodo-1H-indazole-1-carboxylate

HRID 246720

反応式

HRID 246720 の反応式
Br[C:2](P(=O)(OCC)OCC)([F:4])[F:3].[OH:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[N:18]=[C:17]2[I:30].[OH-].[K+]>CC#N.O.CCOC(C)=O>[F:3][CH:2]([F:4])[O:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[N:19]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[N:18]=[C:17]2[I:30]

参加物

6

反応物 3

HCID 14797Potassium HydroxideHCID 144101Bromodifluoromethyl diethylphosphonateHCID 71280823tert-Butyl 5-hydroxy-3-iodo-1H-indazole-1-carboxylate

生成物 1

HCID 71279601tert-butyl 5-(difluoromethoxy)-3-iodo-1H-indazole-1-carboxylate収率 47%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 18373917Acetonitrile--water (1/1)溶媒

実験手順

Diethyl bromodifluoromethylphosphonate (1.13 g, 4.22 mmol) was added in one portion to a cooled (−30° C.) solution of tert-butyl 5-hydroxy-3-iodo-1H-indazole-1-carboxylate and KOH (2.36 g, 42.2 mmol) in MeCN/H2O (20 mL/20 mL). The reaction mixture was allowed to warm to room temperature. After 20 min, the reaction mixture was diluted with EtOAc (15 mL), and the organic phase was separated. The water phase was extracted with EtOAc (10 mL). The combined organic layers were dried over Na2SO4. Evaporation of the solvent gave a crude product that was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1) to give tert-butyl 5-(difluoromethoxy)-3-iodo-1H-indazole-1-carboxylate (0.41 g, 47% over two steps) as a white solid. 1H NMR (300 MHz, CDCl3): δ 8.13 (d, 1H, J=9.0 Hz), 7.39 (dd, 1H, J=9, 2.4 Hz), 7.23 (d, 1H, J=2.4 Hz), 6.57 (t, 1H, J=73.2 Hz), 1.73 (s, 9H).

後処理

  1. customthe organic phase was separated
  2. extractionThe water phase was extracted with EtOAc (10 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. customEvaporation of the solvent
  5. customgave a crude product that
  6. customwas purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1)

出典と根拠

ORDレコード
ord-f47ff4e00fbd4e3f93922ff290baba21
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

関連ノート

読み込み中…