Trifluoroacetic acid → HCID 68671843, compound

HRID 512968Notes

Reaction equation

HRID 512968 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].[CH3:22][N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C:24]1=O.FC(F)(F)C(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>O1CCOCC1>[CH3:21][N:18]1[CH2:19][CH2:20][N:15]([C:13]2[CH:12]=[CH:11][C:3]([C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])=[C:2]([NH:1][CH:26]3[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][CH2:25]3)[CH:14]=2)[CH2:16][CH2:17]1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 13603N-Methyl-2-piperidone2×HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 667359202-Amino-4-(4-methylpiperazin-1-yl) benzoic acid tertbutyl ester

Product 1

HCID 68671843HCID 68671843, compoundYield 51%

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-methylpiperidone (0.72 g, 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 26 hours. During this time extra portions of N-methylpiperidone (0.5 mL, 0.75 eq) and sodium triacetoxyborohydride (1.72 g, 7.73 mmol, 1.5 eq) were added. A saturated aqueous solution of NaHCO3 was then added and the reaction mixture was concentrated under reduced pressure. 10% ammonium hydroxide was added until pH 10 and the aqueous phase was extracted with dichloromethane. The organic phase was washed with brine, dried over Na2SO4 and evaporated under reduced pressure. After purification by chromatography over silica gel (DCM/MeOH/NH3 7% in MeOH 90:8:2) 1.025 g of title compound were obtained as off-white solid (51% yield).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. addition10% ammonium hydroxide was added until pH 10
  3. extractionthe aqueous phase was extracted with dichloromethane
  4. washThe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated under reduced pressure
  7. customAfter purification by chromatography over silica gel (DCM/MeOH/NH3 7% in MeOH 90:8:2) 1.025 g of title compound

Sources & evidence

ORD record
ord-98828f0716b64c91bd0b5bd7342c4ac4
Source dataset
uspto-grants-2015_08
Patent number
US09102662B2

Reaction notes

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