Trifluoroacetic acid → HCID 69748185, compound

HRID 2307403Notes

Reaction equation

HRID 2307403 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([O:10][CH2:11][C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3C(OC(C)(C)C)=O)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[H-].[Na+].[C:26]1([S:32](Cl)(=[O:34])=[O:33])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[F:36][C:37]([F:42])([F:41])[C:38]([OH:40])=[O:39]>CN(C)C=O>[F:36][C:37]([F:42])([F:41])[C:38]([OH:40])=[O:39].[C:26]1([S:32]([N:1]2[C:9]3[C:4](=[C:5]([O:10][CH2:11][C@@H:12]4[CH2:16][CH2:15][CH2:14][NH:13]4)[CH:6]=[CH:7][CH:8]=3)[CH:3]=[N:2]2)(=[O:34])=[O:33])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7369Benzenesulfonyl chlorideHCID 24758Sodium hydrideHCID 60128267HCID 60128267, compound

Product 1

HCID 69748185HCID 69748185, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of t-butyl (2S)-2-[(1H-indazol-4-yloxy)methyl]pyrrolidine-1-carboxylate (0.317 g, 1.0 mmol) in dimethylformamide is treated with sodium hydride (0.08 g, 2.0 mmol, 60% in mineral oil) at room temperature, stirred for 10 min, treated with benzenesulfonyl chloride (0.264 g, 1.5 mmol), stirred for 18 h under nitrogen at room temperature, quenched with water and diluted with ether. The organic phase is separated, washed sequentially with water and brine, dried over MgSO4 and concentrated in vacuo to give a white foam residue. The residue is purified by chromatography (silica gel, EtOAc:hexanes, 15:85) to give a white solid. This solid is dissolved in trifluoroacetic acid at 0° C., stirred at room temperature for 90 min and concentrated in vacuo. The resultant residue is triturated under ether to afford the title compound as a white solid, 300 mg, mp 218-219° C., identified by NMR and mass spectral analyses.

Workup

  1. stirringstirred for 18 h under nitrogen at room temperature
  2. customquenched with water
  3. additiondiluted with ether
  4. customThe organic phase is separated
  5. washwashed sequentially with water and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto give a white foam residue
  9. customThe residue is purified by chromatography (silica gel, EtOAc:hexanes, 15:85)
  10. customto give a white solid
  11. stirringstirred at room temperature for 90 min
  12. concentrationconcentrated in vacuo
  13. customThe resultant residue is triturated under ether

Sources & evidence

ORD record
ord-0fe23fd934124464aeea9c3c14132dab
Source dataset
uspto-grants-2004_12
Patent number
US06831094B2

Reaction notes

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