Ethyl Acetate → 2-{Hydroxy-(3-methoxyphenyl)methyl}cyclooctanone

HRID 1741379Notes

Reaction equation

HRID 1741379 reaction equation
[C:1]1(=[O:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].CC([N-]C(C)C)C.[CH:18](=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=1.C(OCC)(=O)C>C1COCC1.O>[OH:27][CH:18]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=1)[CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:1]1=[O:9]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10403CyclooctanoneHCID 115693-MethoxybenzaldehydeHCID 2724682Lithium diisopropylamide

Product 1

HCID 183672572-{Hydroxy-(3-methoxyphenyl)methyl}cyclooctanoneYield 87.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of cyclooctanone (4.0 g) in THF (40 ml) was added LDA (23 ml, 1.5M solution in cyclohexane) at -78° C. under N2, and then after 30 minutes, a solution of m-anisaldehyde (4.1 g) in THF (10 ml) was added in the solution. After being stirred for 2 hours at the same temperature, the solution was poured into the mixture of ethyl acetate and water. The organic layer was washed with 1N-HCl solution, sat. NaHCO3, and brine, dried over MgSO4, and evaporated in vacuo. The residue was purified by chromatography on silica gel to afford 2-{hydroxy-(3-methoxyphenyl)methyl}cyclooctanone (6.9 g). MS (m/z): 245 (M+ -17) IR (Neat): 3400, 1690 cm-1NMR (CDCl3, δ): 1.0-2.3 (10H, m), 2.8-3.2 (2H, m), 3.3-3.6 (1H, m), 3.79 (3H, s), 4.8-5.0 (1H, m), 6.7-7.0 (3H, m), 7.1-7.3 (1H, m)

Workup

  1. washThe organic layer was washed with 1N-HCl solution, sat. NaHCO3, and brine
  2. dry with materialdried over MgSO4
  3. customevaporated in vacuo
  4. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-bbee8f49808a4aa39652556f97d463e1
Source dataset
uspto-grants-1999_10
Patent number
US05972965

Reaction notes

Loading…