Cyclohexanone → 8-Cyclohexyl-3-(4-nitrophenyl)-8-azabicyclo[3.2.1]oct-2-ene

HRID 1520041Notes

Reaction equation

HRID 1520041 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[N+:15]([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH2:30][CH:29]3[NH:31][CH:26]([CH2:27][CH2:28]3)[CH:25]=2)=[CH:20][CH:19]=1)([O-:17])=[O:16].[C:32]1(=O)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.C([O-])(O)=O.[Na+]>ClCCCl>[CH:32]1([N:31]2[CH:29]3[CH2:28][CH2:27][CH:26]2[CH:25]=[C:24]([C:21]2[CH:20]=[CH:19][C:18]([N+:15]([O-:17])=[O:16])=[CH:23][CH:22]=2)[CH2:30]3)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 7967CyclohexanoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 97945973-(4-Nitrophenyl)-8-azabicyclo[3.2.1]oct-2-ene

Product 1

HCID 679816248-Cyclohexyl-3-(4-nitrophenyl)-8-azabicyclo[3.2.1]oct-2-eneYield 65%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (460 mg, 2.17 mmol, 2.0 eq.) was added to a solution of 3-(4-nitrophenyl)-8-azabicyclo[3.2.1]oct-2-ene (250 mg; 1.1 mmol; 1.0 eq.) and cyclohexanone (168 μl; 1.63 mmol; 1.5 eq.) in DCE (10.00 mL) and the reaction mixture was heated at 500 under nitrogen atmosphere. After 1 h, the reaction mixture was poured into a saturated solution of NaHCO3. Aqueous phase was extracted twice with DCM and combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude was purified by flash chromatography on silica (DCM:MeOH, gradient from 100:0 to 90:10) to give the title compound as a beige solid (220 mg, 65%). 1H NMR (300 MHz, DMSO-d6) δ 8.17 (d, J=8.9 Hz, 2H), 7.68 (d, J=8.9 Hz, 2H), 6.68 (d, J=5.4 Hz, 1H), 3.79-3.68 (m, 2H), 2.80-2.75 (m, 1H), 2.31 (m, 1H), 2.07-1.66 (m, 8H), 1.52 (m, 2H), 1.23-1.09 (m, 5H). HPLC (max plot) 100.0%; Rt %3.01 min. UPLC/MS: (MS+) 313.4.

Workup

  1. temperaturethe reaction mixture was heated at 500 under nitrogen atmosphere
  2. extractionAqueous phase was extracted twice with DCM
  3. washwere washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was purified by flash chromatography on silica (DCM:MeOH, gradient from 100:0 to 90:10)

Sources & evidence

ORD record
ord-18af286035dc4750811e2df398e96266
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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