Trifluoroacetic acid → HCID 68006307, compound

HRID 1026604Notes

Reaction equation

HRID 1026604 reaction equation
[NH2:1][C:2]1[C:3]([S:9][C:10]([CH3:19])([CH3:18])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.O=[C:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]1.FC(F)(F)C(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl>[C:14]([O:13][C:11](=[O:12])[C:10]([S:9][C:3]1[C:2]([NH:1][CH:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)=[CH:7][C:6]([Cl:8])=[CH:5][N:4]=1)([CH3:19])[CH3:18])([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acid2×HCID 14798Sodium HydroxideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate2×HCID 5049666Sodium triacetoxyborohydride2×HCID 68006205HCID 68006205, compound

Product 1

HCID 68006307HCID 68006307, compoundYield 89.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a 1,2-dichloroethane solution (2 ml) of tert-butyl 2-[(3-amino-5-chloropyridin-2-yl)thio]-2-methylpropanoate (334 mg) and tert-butyl 4-oxopiperidine-1-carboxylate (272 mg) was added at room temperature trifluoroacetic acid (0.084 ml), followed by stirring for 15 minutes. Sodium triacetoxyborohydride (356 mg) was added to the reaction solution, and stirred at 45° C. overnight. Cooling to room temperature, tert-butyl 4-oxopiperidine-1-carboxylate (264 mg) and trifluoroacetic acid (0.084 ml) were added. After the reaction solution was stirred for 10 minutes, sodium triacetoxyborohydride (345 mg) was added, and further stirred at 45° C. overnight. After the reaction solution was cooled to room temperature, 1 N aqueous sodium hydroxide solution was added, and extracted with dichloromethane. The collected 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 tert-butyl 4-({2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-5-chloropyridin-3-yl}amino)piperidine-1-carboxylate (478 mg).

Workup

  1. stirringstirred at 45° C. overnight
  2. stirringAfter the reaction solution was stirred for 10 minutes
  3. stirringfurther stirred at 45° C. overnight
  4. temperatureAfter the reaction solution was cooled to room temperature
  5. extractionextracted with dichloromethane
  6. washThe collected organic layer was washed with saturated sodium chloride solution
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-80438a616ce64902b752ebf0437b9482
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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