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

HRID 246720

반응식

HRID 246720 반응식
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]

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 18373917Acetonitrile--water (1/1)용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-f47ff4e00fbd4e3f93922ff290baba21
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

연결된 노트

불러오는 중…