Diisopropylamine → 2-(3-Benzyloxy-4-nitrobenzyl)-cyclohexanone

HRID 660549Notes

Reaction equation

HRID 660549 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]1(=[O:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[CH2:20]([O:27][C:28]1[CH:33]=[C:32]([CH2:34]Br)[CH:31]=[CH:30][C:29]=1[N+:36]([O-:38])=[O:37])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])(O)=O.[Na+]>C1COCC1>[CH2:20]([O:27][C:28]1[CH:33]=[C:32]([CH:31]=[CH:30][C:29]=1[N+:36]([O-:38])=[O:37])[CH2:34][CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18][C:13]1=[O:19])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 7967CyclohexanoneHCID 516892Sodium BicarbonateHCID 621150422-Benzyloxy-4-bromomethyl-1-nitrobenzeneHCID 178418339Butyllithium

Product 1

HCID 688393162-(3-Benzyloxy-4-nitrobenzyl)-cyclohexanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of diisopropylamine (0.44 mL, 3.1 mmol) in THF (5 mL) at 0° C. was added n-butyllithium (1.6 M in hexane, 1.94 mL, 3.1 mmol) dropwise and the solution is stirred for 20 min. After cooling the solution to −78° C., a solution of cyclohexanone (0.32 ml., 3.1 mmol) in THF (2 mL) is added dropwise. The solution is stirred at −78° C. for 1 h then a solution of 2-benzyloxy-4-bromomethyl-1-nitrobenzene (1.0 g, 3.1 mmol) in THF (3 mL) is added dropwise. The solution was warmed to RT and stirred for 18 h. Saturated NaHCO3 is added and the mixture is extracted with EtOAc. The organic layer is washed with water then brine and dried over MgSO4. The solvent is removed under reduced pressure and the residue is purified by flash chromatography using a gradient of 20-33% EtOAc/hexane as eluent to give the title compound as a yellow liquid. NMR (CDCl3): δ 7.79-7.77 (d, J=8.33 Hz, 1H), 7.46-7.31 (m, 5H), 6.93 (d, J=1.51 Hz, 1H), 6.81-6.79 (dd, J=1.52 Hz, 8.34 Hz, 1 H), 5.22 (s, 2H), 3.20-3.16 (m, 1H), 2.53-2.39 (m, 2H), 2.33-2.25 (m, 1H), 2.11-2.05 (m, 1H), 1.96-1.90 (m, 1H), 1.85-1.79 (m, 1H), 1.66-1.55 (m, 2H), 1.35-1.25 (m, 2H).

Workup

  1. stirringThe solution is stirred at −78° C. for 1 h
  2. temperatureThe solution was warmed to RT
  3. stirringstirred for 18 h
  4. extractionthe mixture is extracted with EtOAc
  5. washThe organic layer is washed with water
  6. dry with materialbrine and dried over MgSO4
  7. customThe solvent is removed under reduced pressure
  8. customthe residue is purified by flash chromatography

Sources & evidence

ORD record
ord-9ff00a306b9947afbe2db0472019caae
Source dataset
uspto-grants-2011_12
Patent number
US08084448B2

Reaction notes

Loading…