Triethylamine → 4-Methylpiperazine-1-carboxylic acid [4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl]amide

HRID 492677Notes

Reaction equation

HRID 492677 reaction equation
[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[CH:6]=1.[CH2:19]([N:21]([CH2:24]C)[CH2:22][CH3:23])[CH3:20].ClC([O:29][C:30]1C=CC=CC=1)=O.C[N:37]1CCNCC1>O1CCCC1.C(OCC)(=O)C.CN(C)C=O>[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:30]([N:37]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:19][CH2:20]2)=[O:29])[CH:6]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 531671-MethylpiperazineHCID 231531982-Amino-4-(2-fluoro-4-nitrophenoxy)pyridine

Product 1

HCID 576774434-Methylpiperazine-1-carboxylic acid [4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl]amideYield 99.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(2-fluoro-4-nitrophenoxy)pyridin-2-ylamine (300 mg, 1.2 mmol) and triethylamine (0.335 ml, 2.4 mmol) in tetrahydrofuran (30 ml) was added phenyl chloroformate (0.226 ml, 1.8 mmol) dropwise while stirring in an ice bath, followed by stirring for 1 hr. The reaction mixture was concentrated under a reduced pressure to give a residue, to which was then added N,N-dimethylformamide (6.0 ml) and 1-methylpiperazine (537 μl, 4.84 mmol), followed by stirring at room temperature for 3 hrs. To the reaction mixture was added ethyl acetate (150 ml), washed with a saturated aqueous solution of sodium hydrogencarbonate, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:2, then ethyl acetate) to provide the titled compound (450 mg, 75.3%) as a pale yellow oil.

Workup

  1. stirringby stirring for 1 hr
  2. concentrationThe reaction mixture was concentrated under a reduced pressure
  3. customto give a residue
  4. stirringby stirring at room temperature for 3 hrs
  5. washwashed with a saturated aqueous solution of sodium hydrogencarbonate
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customto give a residue, which
  9. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent

Sources & evidence

ORD record
ord-c9c5aa7b9cdd4d98a6e569edab62b464
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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