Trifluoroacetic acid → Ethyl 4-{[2-(tert-butoxycarbonyl)-5-(4-methylpiperazin-1-yl)phenyl]amino}piperidine-1-carboxylate

HRID 1803862Notes

Reaction equation

HRID 1803862 reaction equation
[NH2:1][C:2]1[CH:14]=[C:13]([N:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)[CH:12]=[CH:11][C:3]=1[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[CH2:22]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][C:28]1=O)=[O:26])[CH3:23].FC(F)(F)C(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>O1CCOCC1>[C:7]([O:6][C:4]([C:3]1[CH:11]=[CH:12][C:13]([N:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)=[CH:14][C:2]=1[NH:1][CH:30]1[CH2:31][CH2:32][N:27]([C:25]([O:24][CH2:22][CH3:23])=[O:26])[CH2:28][CH2:29]1)=[O:5])([CH3:10])([CH3:9])[CH3:8]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 13303317Ethyl 2-oxopiperidine-1-carboxylateHCID 667359202-Amino-4-(4-methylpiperazin-1-yl) benzoic acid tertbutyl ester

Product 1

HCID 66996520Ethyl 4-{[2-(tert-butoxycarbonyl)-5-(4-methylpiperazin-1-yl)phenyl]amino}piperidine-1-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 2-amino-4-(4-methylpiperazin-1-yl)benzoate (1.5 g, 5.15 mmol) was dissolved in dry dioxane (25 mL) under a nitrogen atmosphere. N-ethoxycarbonylpiperidone (1.06 g, 0.932 mL, 6.18 mmol, 1.2 eq) was added, followed by trifluoroacetic acid (1.03 mL, 13.39 mmol, 2.6 eq) and sodium triacetoxyborohydride (1.72 g, 7.73 mmol, 1.5 eq). The mixture was stirred at room temperature for 4 hours. A saturated aqueous solution of NaHCO3 was then added, the mixture was concentrated under reduced pressure and extracted with dichloromethane (3×40 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. After purification by chromatography over silica gel (DCM/EtOH 93:7) 2.187 g of title compound were obtained as a white solid (95% yield).

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. extractionextracted with dichloromethane (3×40 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customAfter purification by chromatography over silica gel (DCM/EtOH 93:7) 2.187 g of title compound

Sources & evidence

ORD record
ord-e3b1ca3bcd0a454aa0180526bbfe0fa7
Source dataset
uspto-grants-2013_01
Patent number
US08354399B2

Reaction notes

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