Trifluoroacetic acid → HCID 68006188, compound

HRID 1026572Notes

Reaction equation

HRID 1026572 reaction equation
[Cl:1][C:2]1[CH:47]=[N:46][C:5]2[O:6][C:7]3([CH2:45][CH2:44]3)[C:8](=[O:43])[N:9]([CH:10]3[CH2:15][CH2:14][N:13]([C:16]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[O:30][CH2:31][C:32]([CH3:41])([CH3:40])[C:33]([O:35]C(C)(C)C)=[O:34])=[CH:20][C:19]=4[CH3:42])=[O:17])[CH2:12][CH2:11]3)[C:4]=2[CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[CH:47]=[N:46][C:5]2[O:6][C:7]3([CH2:45][CH2:44]3)[C:8](=[O:43])[N:9]([CH:10]3[CH2:11][CH2:12][N:13]([C:16]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[O:30][CH2:31][C:32]([CH3:40])([CH3:41])[C:33]([OH:35])=[O:34])=[CH:20][C:19]=4[CH3:42])=[O:17])[CH2:14][CH2:15]3)[C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68006069HCID 68006069, compound

Product 1

HCID 68006188HCID 68006188, compoundYield 74.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a dichloromethane solution (13 ml) of tert-butyl 3-[(4′-{[4-(7′-Chloro-2′-oxospiro[cyclopropane-1,3′-pyrido[2,3-b][1,4]oxazin]-1′(2′H)-yl)piperidin-1-yl]carbonyl}-3′-methylbiphenyl-2-yl)oxy]-2,2-dimethylpropanoate (642 mg) was added at room temperature trifluoroacetic acid (6.5 ml), followed by stirring overnight. After the reaction solution was concentrated under reduced pressure, a saturated aqueous sodium hydrogen carbonate solution was added to the residue for neutralization, and then a 10% aqueous citric acid solution was added, and extracted with dichloromethane. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 3-[(4′-{[4-(7′-chloro-2′-oxospiro[cyclopropane-1,3′-pyrido[2,3-b][1,4]oxazin]-1′(2′H)-yl)piperidin-1-yl]carbonyl}-3′-methylbiphenyl-2-yl)oxy]-2,2-dimethylpropanoic acid (440 mg).

Workup

  1. concentrationAfter the reaction solution was concentrated under reduced pressure
  2. additiona saturated aqueous sodium hydrogen carbonate solution was added to the residue for neutralization
  3. additiona 10% aqueous citric acid solution was added
  4. extractionextracted with dichloromethane
  5. washThe organic layer was washed with saturated sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3b1eaef224994a3e8bb7a5243ee0984f
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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