Triethylamine → t-Butyl 4-[4-(2-fluoro-4-nitrophenoxy)pyridin-2-ylcarbamoyl]piperidine-1-carboxylate

HRID 492679Notes

Reaction equation

HRID 492679 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.[C:19]([N:26]1[CH2:34][CH2:33][CH:29]([C:30](O)=[O:31])[CH2:28][CH2:27]1)([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C.CCCCCC>[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]([CH:29]2[CH2:33][CH2:34][N:26]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:27][CH2:28]2)=[O:31])[CH:6]=1

Participants

8

Reactant 4

HCID 8471Triethylamine3×HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate3×HCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid3×HCID 231531982-Amino-4-(2-fluoro-4-nitrophenoxy)pyridine

Product 1

HCID 23153115t-Butyl 4-[4-(2-fluoro-4-nitrophenoxy)pyridin-2-ylcarbamoyl]piperidine-1-carboxylateYield 73.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

To a solution of 4-(2-fluoro-4-nitrophenoxy)pyridin-2-ylamine (400 mg, 1.61 mmol) in N,N-dimethylformamide (16 ml) were added Boc-isonipecotic acid (554 mg, 2.42 mmol), triethylamine (0.673 ml, 4.83 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.07 g, 2.42 mmol), followed by stirring at room temperature for 6.5 hrs. Boc-isonipecotic acid (554 mg, 2.42 mmol), triethylamine (0.673 ml, 4.83 mmol), and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.07 g, 2.42 mmol) were further added thereto, followed by stirring at room temperature for 3 hrs. Furthermore, Boc-isonipecotic acid (554 mg, 2.42 mmol), triethylamine (0.673 ml, 4.83 mmol), and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.07 g, 2.42 mmol) were added thereto, followed by stirring at room temperature for 3 days. 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 subjected to silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:1, then ethyl acetate) to provide a crude product of the titled compound (548 mg) as a yellow oil.

Workup

  1. stirringby stirring at room temperature for 3 hrs
  2. stirringby stirring at room temperature for 3 days
  3. washwashed with a saturated aqueous solution of sodium hydrogencarbonate
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. customto give a residue, which

Sources & evidence

ORD record
ord-05741a6915ed410980f689e73a8a935d
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

Loading…