4-Aminomethyltetrahydropyran → Methyl {3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}carbamate

HRID 472942Notes

Reaction equation

HRID 472942 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:12])[O:10][CH3:11])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].[NH2:16][CH2:17][CH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1>CCO>[N+:13]([C:3]1[CH:4]=[C:5]([NH:8][C:9](=[O:12])[O:10][CH3:11])[CH:6]=[CH:7][C:2]=1[NH:16][CH2:17][CH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)([O-:15])=[O:14]

Participants

4

Reactant 2

HCID 27732104-AminomethyltetrahydropyranHCID 3636899Methyl (4-fluoro-3-nitrophenyl)carbamate

Product 1

HCID 57723218Methyl {3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}carbamate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methyl (4-fluoro-3-nitrophenyl)carbamate (2.0 g, 9.32 mmol) and 4-aminomethyl tetrahydropyran (1.28 g, 11.2 mmol) were stirred in 50 mL of EtOH containing TEA (2.0 mL, 14.0 mmol) at 75° C. for 48 h. The solvent was evaporated. The residue was dissolved in EtOAc and washed with aqueous 5% KHSO4, saturated aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. The crude product was purified by silica gel flash chromatography using 1:1/hexanes:EtOAc as eluent. Yield: 2.53 g (88%). 1H NMR (400 MHz, CHLOROFORM-D): δ 1.42 (ddd, J=25.24, 12.06, 4.49 Hz, 2H), 1.73 (d, J=1.76 Hz, 1H), 1.76 (d, J=1.95 Hz, 1H), 1.88-2.01 (m, 1H), 3.22 (dd, J=6.74, 5.57 Hz, 2H), 3.42 (td, J=11.86, 2.05 Hz, 2H), 3.78 (s, 3 H), 4.01 (d, J=4.30 Hz, 1H), 4.04 (d, J=3.51 Hz, 1H), 6.48 (br.s, 1H), 6.85 (d, J=9.37 Hz, 1H), 7.65 (br.s, 1H), 8.03-8.09 (m, 2H).

Workup

  1. customThe solvent was evaporated
  2. dissolutionThe residue was dissolved in EtOAc
  3. washwashed with aqueous 5% KHSO4, saturated aqueous NaHCO3 solution, brine
  4. dry with materialdried over anhydrous MgSO4
  5. customThe crude product was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-297db073d2e6437ead5ed4210f89dfe1
Source dataset
uspto-grants-2014_01
Patent number
US08633235B2

Reaction notes

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