Sodium Bicarbonate → Methyl 1-(4-(6-bromo-3-nitroquinolin-4-ylamino)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate

HRID 1944610Notes

Reaction equation

HRID 1944610 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([N+:12]([O-:14])=[O:13])=[C:5]2Cl.[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][CH:26]([C:29]([O:31][CH3:32])=[O:30])[CH2:25][CH2:24]2)=[C:19]([C:33]([F:36])([F:35])[F:34])[CH:18]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([N+:12]([O-:14])=[O:13])=[C:5]2[NH:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][CH:26]([C:29]([O:31][CH3:32])=[O:30])[CH2:25][CH2:24]2)=[C:19]([C:33]([F:36])([F:34])[F:35])[CH:18]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 219841286-Bromo-4-chloro-3-nitroquinolineHCID 67007713Methyl 1-(4-amino-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate

Product 1

HCID 67008148Methyl 1-(4-(6-bromo-3-nitroquinolin-4-ylamino)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylateYield 90.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of compound 8.0 6-bromo-4-chloro-3-nitroquinoline (0.29 g, 1.0 mmol, 1 equiv.) in dioxane (5 mL) at room temperature was added 8.1 methyl 1-(4-amino-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate (0.3 g, 1.0 mmol, 1 equiv.). The resulting mixture was heated overnight to 85° C. under argon. Upon cooling to room temperature, the mixture was neutralized with aqueous NaHCO3, diluted with EtOAc (50 mL), and washed with water (50 mL) and brine (50 mL). The organic phase was dried over Na2SO4. After removal of solvent under vacuum, the resulting residue was purified via flash chromatography (Hexanes: EtOAc=4:1) to afford desired product 8.2 methyl 1-(4-(6-bromo-3-nitroquinolin-4-ylamino)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate (0.50 g; 90%). LC-MS (M+H): 555.10

Workup

  1. temperatureThe resulting mixture was heated overnight to 85° C. under argon
  2. washwashed with water (50 mL) and brine (50 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. customAfter removal of solvent under vacuum
  5. customthe resulting residue was purified via flash chromatography (Hexanes: EtOAc=4:1)

Sources & evidence

ORD record
ord-b450ac1881504b86af534a3beee8172f
Source dataset
uspto-grants-2013_03
Patent number
US08394818B2

Reaction notes

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