Tetrabutylammonium Fluoride → Methyl 3-[[2-fluoro-5-[3-(hydroxymethyl)-1-piperidyl]benzoyl]amino]-2,4-dimethyl-benzoate

HRID 239930Notes

Reaction equation

HRID 239930 reaction equation
[Si]([O:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]2[CH:17]=[CH:18][C:19]([F:37])=[C:20]([CH:36]=2)[C:21]([NH:23][C:24]2[C:25]([CH3:35])=[C:26]([CH:31]=[CH:32][C:33]=2[CH3:34])[C:27]([O:29][CH3:30])=[O:28])=[O:22])[CH2:11]1)(C(C)(C)C)(C)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[F-]>C1COCC1>[F:37][C:19]1[CH:18]=[CH:17][C:16]([N:12]2[CH2:13][CH2:14][CH2:15][CH:10]([CH2:9][OH:8])[CH2:11]2)=[CH:36][C:20]=1[C:21]([NH:23][C:24]1[C:25]([CH3:35])=[C:26]([CH:31]=[CH:32][C:33]=1[CH3:34])[C:27]([O:29][CH3:30])=[O:28])=[O:22]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86707316Methyl 3-[[5-[3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-piperidyl]-2-fluoro-benzoyl]amino]-2,4-dimethyl-benzoate

Product 1

HCID 86707317Methyl 3-[[2-fluoro-5-[3-(hydroxymethyl)-1-piperidyl]benzoyl]amino]-2,4-dimethyl-benzoateYield 16.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyl 3-[[5-[3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-piperidyl]-2-fluoro-benzoyl]amino]-2,4-dimethyl-benzoate (2.9 g, 5.48 mmol) in THF (20 ml) is added Bu4NF 1.0 M in THF (5.73 g, 0.0219 mol) at 0° C. The reaction mixture is gradually warmed to ambient temperature. After 4 hours, the reaction mixture is diluted with ice-water and extracted with ethyl acetate. The organic layers are combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a residue. The residue is purified by flash chromatography (silica gel) over a gradient using 35-45% ethyl acetate in hexane to afford the title compound as a white solid (0.38 g, 16.8%). Mass spectrum (m/z): 415.2 (M+1).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give a residue
  6. customThe residue is purified by flash chromatography (silica gel) over a gradient

Sources & evidence

ORD record
ord-f9b20602a8fd43d7b3a3d8328cd7004d
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Reaction notes

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