Hydrochloric Acid → 1-(1-Allyl-5-hydroxymethyl-1H-pyrrol-3-yl)-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol

HRID 244435Notes

Reaction equation

HRID 244435 reaction equation
C([O:3][C:4]([C:6]1[N:7]([CH2:33][CH:34]=[CH2:35])[CH:8]=[C:9]([C:11]([C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[N:22]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[N:21]=[CH:20]3)([OH:16])[C:12]([F:15])([F:14])[F:13])[CH:10]=1)=O)C.[H-].C([Al+]CC(C)C)C(C)C.Cl.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH2:33]([N:7]1[C:6]([CH2:4][OH:3])=[CH:10][C:9]([C:11]([C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[N:22]([C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[N:21]=[CH:20]3)([OH:16])[C:12]([F:15])([F:14])[F:13])=[CH:8]1)[CH:34]=[CH2:35]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 21225700DiisobutylaluminumhydrideHCID 249590981-allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carboxylic acid ethyl ester

Product 1

HCID 249616531-(1-Allyl-5-hydroxymethyl-1H-pyrrol-3-yl)-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanolYield 4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a chilled (0° C.) solution of 250 mg (0.51 mmol) 1-allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carboxylic acid ethyl ester in anhydrous CH2Cl2 was added 1.5 mL (1.5 mmol) of a 1 M solution of diisobutylaluminum hydride (DIBAL) in CH2Cl2. The reaction was warmed to reflux and stirred overnight. The reaction was cooled to room temperature, poured into 100 mL of 1N aqueous HCl, then made basic with saturated aqueous sodium bicarbonate, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by HPLC using CH3CN—H2O buffered with 0.1% TFA (5-90% gradient). The fractions from the column were concentrated in vacuo to remove CH3CN and then the resulting aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate. The solvent was concentrated in vacuo to afford 8.0 mg (4%) of the title compound. MS m/z 446.41 (MH+).

Workup

  1. temperatureThe reaction was warmed
  2. temperatureto reflux
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by HPLC
  8. concentrationThe fractions from the column were concentrated in vacuo
  9. customto remove CH3CN
  10. extractionthe resulting aqueous layer was extracted with ethyl acetate
  11. washThe combined organic layers were washed with brine
  12. dry with materialdried over sodium sulfate
  13. concentrationThe solvent was concentrated in vacuo

Sources & evidence

ORD record
ord-c321db25cba9452e953e4b0c520639b4
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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