Hydrochloric Acid → 4-(4-(Benzyloxy)phenyl)-4-(2-fluorophenyl)cyclohex-2-enone

HRID 2174432Notes

Reaction equation

HRID 2174432 reaction equation
[OH-].[K+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[F:26])[CH:18]=O)=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH:27]([C:29]([CH3:31])=[O:30])=[CH2:28].Cl>CCO.C1COCC1.CCOCC>[CH2:3]([O:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[CH2:18][CH2:31][C:29](=[O:30])[CH:27]=[CH:28]2)=[CH:15][CH:16]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6570Methyl vinyl ketoneHCID 14797Potassium HydroxideHCID 894003632-(4-(Benzyloxy)phenyl)-2-(2-fluorophenyl)acetaldehyde

Product 1

HCID 712451374-(4-(Benzyloxy)phenyl)-4-(2-fluorophenyl)cyclohex-2-enoneYield 98.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of KOH (110 mg, 2.0 mmol) in EtOH (3 mL) was added at 0° C. to a stirred solution of 4 (2.52 g, 7.9 mmol) and methyl vinyl ketone (0.61 g, 8.7 mmol) in THF (60 mL). The resulting mixture was stirred at room temperature overnight. Ether (200 mL) and HCl (50 mL, 10% aqueous solution) were added. The organic phase was washed with HCl (50 mL, 10% aqueous solution), H2O (50 mL), NaHCO3 (50 mL, saturated aqueous solution), dried over Na2SO4 and evaporated under reduced pressure. The crude material was dissolved in EtOH (40 mL) and HCl (2 mL, 37% aqueous solution) was added. The mixture was heated at 50° C. for 30 min under stirring. After cooling to room temperature, H2O (50 mL) was added. The mixture was extracted with diethyl ether (3×100 mL) and the combined organic phase was washed with NaHCO3 (2×50 mL, saturated aqueous solution) and brine (50 mL), dried over Na2SO4 and evaporated under reduced pressure to yield 2.89 g crude material. Purification by column chromatography (heptane:ethyl acetate 4:1 to 2:1) yielded 2.41 g, 82% as an off-white solid. 1H-NMR (CDCl3) δ; 7.44-7.35 (m, 6H), 7.35-7.28 (m, 2H), 7.17 (dt, 1H, J=7.5 Hz and 1.4 Hz), 7.11 (d, 2H, J=8.9 Hz), 7.02 (dd, 1H, J=7.0 Hz and 1.4 Hz), 6.92 (d, 2H, J=8.9 Hz), 6.19 (d, 1H, J=10.3 Hz), 5.04 (s, 2H), 2.90-2.81 (m, 1H), 2.62-2.52 (m, 1H), 2.44 (at, 2H, J=6.6 Hz); 13C-NMR (CDCl3) δ; 199.0, 161.3 (d, J=249.6 Hz), 157.9, 154.9 (d, J=3.8 Hz), 137.1 (d, J=12.1 Hz), 132.0 (d, J=10.8 Hz), 129.5 (d, J=8.8 Hz), 129.3, 128.8, 128.7 (d, J=4.2 Hz), 128.2, 128.1, 127.7, 124.3 (d, J=3.5 Hz), 117.2 (d, J=22.7), 115.0, 70.3, 47.3 (d, J=1.9 Hz), 35.1, 35.0;

Workup

  1. washThe organic phase was washed with HCl (50 mL, 10% aqueous solution), H2O (50 mL), NaHCO3 (50 mL, saturated aqueous solution)
  2. dry with materialdried over Na2SO4
  3. customevaporated under reduced pressure
  4. dissolutionThe crude material was dissolved in EtOH (40 mL)
  5. additionHCl (2 mL, 37% aqueous solution) was added
  6. temperatureThe mixture was heated at 50° C. for 30 min
  7. stirringunder stirring
  8. temperatureAfter cooling to room temperature
  9. additionH2O (50 mL) was added
  10. extractionThe mixture was extracted with diethyl ether (3×100 mL)
  11. washthe combined organic phase was washed with NaHCO3 (2×50 mL, saturated aqueous solution) and brine (50 mL)
  12. dry with materialdried over Na2SO4
  13. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-8dacbd41a0434bf8b1a441739900ca14
Source dataset
uspto-grants-2015_06
Patent number
US09061981B2

Reaction notes

Loading…