Diisopropylethylamine → 1,1-Dimethylethyl 4-{[5-methyl-4-methoxy-2-nitrophenyl]amino}-1-piperidinecarboxylate

HRID 2064136Notes

Reaction equation

HRID 2064136 reaction equation
F[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[NH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.C(N(C(C)C)CC)(C)C>>[CH3:8][C:6]1[C:5]([O:9][CH3:10])=[CH:4][C:3]([N+:11]([O-:13])=[O:12])=[C:2]([NH:14][CH:15]2[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20]2)[CH:7]=1

Participants

4

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 12682914-Amino-1-Boc-piperidine2×HCID 598501391-Fluoro-4-methoxy-5-methyl-2-nitrobenzene

Product 1

HCID 598501341,1-Dimethylethyl 4-{[5-methyl-4-methoxy-2-nitrophenyl]amino}-1-piperidinecarboxylate

Conditions

Temperature
75 °C

Procedure

1-Fluoro-5-methyl-4-methoxy-2-nitrobenzene (D17) (0.79 mmol, 146 mg) was treated under argon at room temperature with 1,1-dimethylethyl 4-amino-1-piperidinecarboxylate (0.8 mmol, 160 mg, 1 eq) and diisopropylethylamine (0.8 mmol, 103 mg, 1 eq) then stirred at 75° C. overnight. Completion was not observed, and the mixture was heated at higher temperature, 1,1-dimethylethyl 4-amino-1-piperidinecarboxylate (0.8 mmol, 160 mg, 1 eq) and diisopropylethylamine (0.8 mmol, 103 mg, 1 eq) were added again and allowed to react overnight at 100° C. The mixture was concentrated under reduced pressure, treated with 10% Na2CO3 aqueous solution and extracted twice with ether. Organics were combined, dried on MgSO4, concentrated under reduced pressure and chromatographed (0-50% ethyl acetate/petrol ether) to give the title compound as an orange residue (0.33 mmol, 120 mg, 42% yield). M+H=310.1, main fragment (molecule has lost its tert-butyl group).

Workup

  1. additionwere added again
  2. customto react overnight at 100° C
  3. concentrationThe mixture was concentrated under reduced pressure
  4. additiontreated with 10% Na2CO3 aqueous solution
  5. extractionextracted twice with ether
  6. customdried on MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customchromatographed (0-50% ethyl acetate/petrol ether)

Sources & evidence

ORD record
ord-adf7391d1a424d668da29b9136825f11
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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