tert-butyl 3-{[3'-fluoro-4'-({4-[(3S)-7-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl]piperidin-1-yl}carbonyl)biphenyl-2-yl]oxy}-2,2-dimethylpropanoate → 3-{[3'-fluoro-4'-({4-[(3S)-7-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl]piperidin-1-yl}carbonyl)biphenyl-2-yl]oxy}-2,2-dimethylpropanoic acid

HRID 1026561Notes

Reaction equation

HRID 1026561 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[O:35][CH2:36][C:37]([CH3:46])([CH3:45])[C:38]([O:40]C(C)(C)C)=[O:39])[CH:5]=[CH:6][C:7]=1[C:8]([N:10]1[CH2:15][CH2:14][CH:13]([N:16]2[C:21](=[O:22])[C@H:20]([CH3:23])[O:19][C:18]3[N:24]=[CH:25][C:26]([F:28])=[CH:27][C:17]2=3)[CH2:12][CH2:11]1)=[O:9]>FC(F)(F)C(O)=O>[F:1][C:2]1[CH:3]=[C:4]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[O:35][CH2:36][C:37]([CH3:45])([CH3:46])[C:38]([OH:40])=[O:39])[CH:5]=[CH:6][C:7]=1[C:8]([N:10]1[CH2:15][CH2:14][CH:13]([N:16]2[C:21](=[O:22])[C@H:20]([CH3:23])[O:19][C:18]3[N:24]=[CH:25][C:26]([F:28])=[CH:27][C:17]2=3)[CH2:12][CH2:11]1)=[O:9]

Participants

3

Reactant 1

HCID 68005985tert-butyl 3-{[3'-fluoro-4'-({4-[(3S)-7-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl]piperidin-1-yl}carbonyl)biphenyl-2-yl]oxy}-2,2-dimethylpropanoate

Product 1

HCID 680063803-{[3'-fluoro-4'-({4-[(3S)-7-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl]piperidin-1-yl}carbonyl)biphenyl-2-yl]oxy}-2,2-dimethylpropanoic acidYield 77.9%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A trifluoroacetic acid solution (10 ml) of tert-butyl 3-{[3′-fluoro-4′-({4-[(3S)-7-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl]piperidin-1-yl}carbonyl)biphenyl-2-yl]oxy}-2,2-dimethylpropanoate (940 mg) was stirred at room temperature for 1 hour. After the reaction solution was concentrated under reduced pressure, the resulting residue was neutralized with a saturated aqueous sodium hydrogen carbonate solution, and then a 10% aqueous citric acid solution was added, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Ethyl acetate-hexane was added to the residue to collect the precipitate by filtration. This was redissolved in ethanol, to which water was added, and the resulting precipitate was collected by filtration to afford 3-{[3′-fluoro-4′-({4-[(3S)-7-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl]piperidin-1-yl}carbonyl)biphenyl-2-yl]oxy}-2,2-dimethylpropanoic acid (668 mg).

Workup

  1. concentrationAfter the reaction solution was concentrated under reduced pressure
  2. additiona 10% aqueous citric acid solution was added
  3. extractionfollowed by extraction with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. additionEthyl acetate-hexane was added to the residue
  7. customto collect the precipitate
  8. filtrationby filtration
  9. dissolutionThis was redissolved in ethanol, to which water
  10. additionwas added
  11. filtrationthe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-43101316889e47fea665c13e5fd9289b
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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