Trifluoroacetic acid → HCID 68006298, compound

HRID 1026551Notes

Reaction equation

HRID 1026551 reaction equation
[NH2:1][C:2]1[C:3](/[CH:9]=[CH:10]/[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.FC(F)(F)C(O)=O.O=[C:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>ClCCl>[Cl:8][C:6]1[CH:7]=[C:2]([NH:1][CH:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)[C:3]([CH2:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:4][CH:5]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 68105235HCID 68105235, compound

Product 1

HCID 68006298HCID 68006298, compoundYield 80.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a dichloromethane (377 ml) solution of ethyl (2E)-3-(3-amino-5-chloropyridin-2-yl)acrylate (37.7 g) and trifluoroacetic acid (12.7 ml) was added tert-butyl 4-oxopiperidine-1-carboxylate (49.7 g). After stirring at room temperature for 15 minutes, sodium triacetoxyborohydride (70.5 g) was added, and stirred at 40° C. for 1.5 hours. After the reaction solution was brought back to room temperature, dichloromethane and a saturated aqueous sodium hydrogen carbonate solution were added and the solution was separated, and the aqueous layer was extracted with dichloromethane. The collected organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was dissolved in methanol (2 ml), and 1.7% palladium-fibroin (10 g) was added, followed by stirring at room temperature for 18 hours under a hydrogen atmosphere. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford tert-butyl 4-{[5-chloro-2-(3-ethoxy-3-oxopropyl)pyridin-3-yl]amino}piperidine-1-carboxylate (55.3 g).

Workup

  1. stirringstirred at 40° C. for 1.5 hours
  2. customwas brought back to room temperature
  3. customthe solution was separated
  4. extractionthe aqueous layer was extracted with dichloromethane
  5. dry with materialThe collected organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe resulting residue was dissolved in methanol (2 ml)
  8. addition1.7% palladium-fibroin (10 g) was added
  9. stirringby stirring at room temperature for 18 hours under a hydrogen atmosphere
  10. filtrationThe reaction solution was filtered
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0999caf602bb4cd1bb8c6de0d3440cac
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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