2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone → 2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-indazol-3-yl)ethanol

HRID 244393Notes

Reaction equation

HRID 244393 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][N:3]=1.[Li]CCCC.[Li]C(C)(C)C.[F:21][C:22]([F:42])([F:41])[C:23]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)[N:29]=[CH:28]2)=[O:24]>CCOCC.CCCCC.[Cl-].[NH4+]>[F:42][C:22]([F:21])([F:41])[C:23]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)[N:29]=[CH:28]2)([C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][N:3]=1)[OH:24]

Participants

8

Reactant 4

HCID 579432692,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanoneHCID 178418306HCID 178418306, compoundHCID 178418339ButyllithiumHCID 178419483HCID 178419483, compound

Product 1

HCID 1785193262,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-indazol-3-yl)ethanolYield 19.6%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 8003PentaneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a chilled (−78° C.) solution of 97 mg (0.49 mmol) of 3-bromo-1H-indazole in 5 mL of anhydrous ether was added 195 μL (0.49 mmol) of a 2.5 M solution of n-BuLi in hexanes dropwise. After 5 minutes, 590 μL (1.0 mmol) of a 1.7 M solution of tert-BuLi in pentane was added dropwise. The mixture stirred for 15 minutes and then a solution of 151 mg (0.49 mmol) of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone in 3 mL of ether was added dropwise. After 1 hour, the reaction was monitored by thin layer chromatography (30% ethyl acetate-hexanes) and LCMS. The mixture was diluted with 10 mL of saturated aqueous ammonium chloride and extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with three 10 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was chromatographed on silica gel using dichloromethane-hexanes (1:1) to load the sample and then eluting with dichloromethane-hexanes (1:1, then 100:0) followed by ethyl acetate-hexanes (2:8). The material from the column was triturated with ether-hexanes to afford 41 mg (19%) of the title compound. MS m/z 427.20 (MH+).

Workup

  1. waitAfter 1 hour
  2. extractionextracted with three 10 mL portions of ethyl acetate
  3. washThe combined organic layers were washed with three 10 mL portions of brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was chromatographed on silica gel
  8. washeluting with dichloromethane-hexanes (1:1
  9. customThe material from the column was triturated with ether-hexanes

Sources & evidence

ORD record
ord-a549e822317440909f4b0b9923e1ca38
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

Loading…