Diisopropylethylamine → Tert-butyl 4-[(4-fluoro-5-methyl-2-nitrophenyl)amino]piperidine-1-carboxylate

HRID 2064138Notes

Reaction equation

HRID 2064138 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5](F)=[CH:4][C:3]=1[CH3:12].[NH2:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[F:1][C:2]1[C:3]([CH3:12])=[CH:4][C:5]([NH:13][CH:14]2[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]2)=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2306581,4-Difluoro-2-methyl-5-nitrobenzeneHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 51072029Tert-butyl 4-[(4-fluoro-5-methyl-2-nitrophenyl)amino]piperidine-1-carboxylateYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1,4-Difluoro-2-methyl-5-nitrobenzene (1.5 mol, 260 mg) in dimethylformamide (10 mL) was treated under argon at room temperature with 1,1-dimethylethyl 4-amino-1-piperidinecarboxylate (1.5 mmol, 300.5 mg, 1 eq) and diisopropylethylamine (1.5 mmol, 260 μL, 1 eq) then stirred at 70 (→80) ° C. for 38 h. The mixture was concentrated under vacuum, treated with water and extracted twice with ether. Organics were combined, dried on MgSO4 and concentrated under vacuum to give a red-brown residue which was chromatographed (0-25% ethyl acetate/petrol ether 6 CV) to give the title compound as a red solid (0.96 mmol, 340 mg, 64% yield). M+H=298.07, main fragment (molecule has lost its tert-butyl group).

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. additiontreated with water
  3. extractionextracted twice with ether
  4. customdried on MgSO4
  5. concentrationconcentrated under vacuum
  6. customto give a red-brown residue which
  7. customwas chromatographed (0-25% ethyl acetate/petrol ether 6 CV)

Sources & evidence

ORD record
ord-b41cea0ca30c4503b6b0d64f4551a23d
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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