Methyl iodide → 7-Methyl-1,4-dioxaspiro[4.5]decan-8-one

HRID 1830837Notes

Reaction equation

HRID 1830837 reaction equation
[NH2-].[Na+].[CH2:3]1[O:13][C:6]2([CH2:11][CH2:10][C:9](=[O:12])[CH2:8][CH2:7]2)[O:5][CH2:4]1.[CH3:14]I.[Cl-].[NH4+]>C1COCC1>[CH2:3]1[CH2:4][O:5][C:6]2([CH2:7][CH2:8][C:9](=[O:12])[CH:10]([CH3:14])[CH2:11]2)[O:13]1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24533Sodium amideHCID 25517Ammonium ChlorideHCID 5674151,4-Dioxaspiro[4.5]decan-8-one

Product 1

HCID 2706287-Methyl-1,4-dioxaspiro[4.5]decan-8-oneYield 74.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
20 °C

Procedure

According to the process described in Tetrahedron, 47, 1991, 3259, a solution of sodium amide (18.5 g) in THF (100 ml) was added to a solution of 1,4-cyclohexanedione monoethylene ketal (18.5 g) in THF (100 ml) under a nitrogen atmosphere while keeping the temperature of the solution at 10–20° C. After stirring at 20° C. for 30 minutes, methyl iodide (41.3 g) was added and the stirring was continued at room temperature for 1 hour. The reaction solution was mixed with a saturated aqueous solution of ammonium chloride (100 ml) and extracted with diethyl ether. The diethyl ether layer was washed with water, dried (MgSO4), and then evaporated under reduced pressure to remove the solvent. The residue was subjected to column chromatography on silica gel and an oily mixture (mixture ratio of 1:1, 15.1 g) of 4,4-ethylenedioxy-2-methyl-1-cyclohexanone and 4,4-ethylenedioxy-2,2-dimethyl-1-cyclohexanone was obtained from the eluates with ethyl acetate-hexane (4:1). To a solution of this mixture (2.0 g) in ethanol (20 ml) was added sodium borohydride (440 mg) under ice cooling. After stirring at room temperature for 2 hours, acetic acid (0.2 ml) was added, and the mixture was evaporated under reduced pressure to remove the solvent. To the residue was added ethyl acetate and the resulting solution was washed with water, dried (MgSO4), and then evaporated under reduced pressure to remove the solvent. The residue was subjected to column chromatography on silica gel to obtain 4-hydoxy-3-methyl-1-cyclohexanone ethylene ketal (140 mg, 1H NMR (CDCl3) δ: 1.02 (3H, d, J=6.6 Hz), 1.20–2.00 (8H, m), 3.15–3.30 (1H, m), 3.94 (4H, br s)) and 4-hydoxy-3,3-dimethyl-1-cyclohexanone ethylene ketal (470 mg, 1H NMR (CDCl3) δ: 1.00 (3H, s), 1.01 (3H, s), 1.35–1.90 (7H, m), 3.38–3.46 (1H, m), 3.90–4.00 (4H, m)) from the eluates with ethyl acetate-hexane (6:1) as oily substances, respectively.

Workup

  1. customat 10–20° C
  2. waitthe stirring was continued at room temperature for 1 hour
  3. extractionextracted with diethyl ether
  4. washThe diethyl ether layer was washed with water
  5. dry with materialdried (MgSO4)
  6. customevaporated under reduced pressure
  7. customto remove the solvent

Sources & evidence

ORD record
ord-34f63d7ed6704b3eb33156ba07082e75
Source dataset
uspto-grants-2006_06
Patent number
US07067527B2

Reaction notes

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