Hydrochloric Acid → 2-(4-Methoxyphenyl)cyclohexanone

HRID 418913

Reaction equation

HRID 418913 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[C:10]1(=[O:16])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.CC(C)([O-])C.[Na+].Cl>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15][C:10]2=[O:16])=[CH:3][CH:4]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 77304-BromoanisoleHCID 7967CyclohexanoneHCID 23676156Sodium t-butoxide

Product 1

HCID 2542922-(4-Methoxyphenyl)cyclohexanoneYield 38.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

Combine 4-bromoanisole (19.6 g, 104 mmol), cyclohexanone (13.2 g, 136 mmol), sodium tert-butoxide (11.8 g, 120 mmol), palladium acetate (0.47 g, 2.1 mmol), (oxy-di-2,1-phenylene)bis-diphenylphosphine (2.28 g, 4.1 mmol) and toluene (240 mL) and heated at 90° C. under nitrogen. After 18 hours, cool to room temperature and add 1N HCl (120 mL). Extract with methylene chloride and wash the combined extracts with brine. Dry the organic layer over sodium sulfate and concentrate in vacuo. Purify by flash chromatography using silica gel and 10% ethyl acetate-hexanes to yield the titled compound (8.15 g, 38%) as a white solid. 1H NMR (CDCl3) δ 7.12 (d, 2H, J=7.5 Hz), 6.92 (d, 2H, J=7.5 Hz), 3.84 (s, 3 H), 3.59 (dd, 1H, J=8.0 and 3.5 Hz), 2.60-2.45 (m, 2H), 2.29 (m, 1H), 2.18 (m, 1H), 2.04 (m, 2H), 1.85 (m, 2H). MS m/z 205 (M+1).

Workup

  1. extractionExtract with methylene chloride
  2. washwash the combined extracts with brine
  3. dry with materialDry the organic layer over sodium sulfate
  4. concentrationconcentrate in vacuo
  5. customPurify by flash chromatography

Sources & evidence

ORD record
ord-3913baa3e50e4a58b0542ab5d19ebd54
Source dataset
uspto-grants-2012_01
Patent number
US08093302B2

Linked notes

Loading…