Hydrochloric Acid → 8-[2,4-Bis(methoxymethoxy)phenyl]-1,4-dioxaspiro[4.5]decan-8-ol

HRID 1007958Notes

Reaction equation

HRID 1007958 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][O:10][CH3:11])=[CH:4][C:3]=1[O:12][CH2:13][O:14][CH3:15].CN(C)CCN(C)C.C([Li])CCC.[CH2:29]1[O:39][C:32]2([CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]2)[O:31][CH2:30]1.Cl>C1COCC1.C(OCC)(=O)C>[CH3:15][O:14][CH2:13][O:12][C:3]1[CH:4]=[C:5]([O:8][CH2:9][O:10][CH3:11])[CH:6]=[CH:7][C:2]=1[C:35]1([OH:38])[CH2:36][CH2:37][C:32]2([O:39][CH2:29][CH2:30][O:31]2)[CH2:33][CH2:34]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 113917541-Bromo-2,4-bis(methoxymethoxy)benzeneHCID 178418339Butyllithium

Product 1

HCID 121351678-[2,4-Bis(methoxymethoxy)phenyl]-1,4-dioxaspiro[4.5]decan-8-olYield 56%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A round bottomed flask was loaded with 1-bromo-2,4-bis(methoxymethoxy)benzene (2.00 g) and THF (50 mL). N,N,N′,N′-Tetramethylethylene diamine (2.3 ml) was added and the solution was cooled to −78° C. n-Butyl lithium (9.5 ml, 1.6M in hexane) was added. The resulting solution was stirred for 1 hr at −78° C. and 1,4-cyclohexanedione monoethylene ketal (1.35 g) was added as a solution in THF (25 ml). The resulting solution was stirred at −78° C. for 1 hr and then allowed to warm to room temperature overnight. Hydrochloric acid (20 ml, 2M) was added and the reaction mixture stirred vigorously for 15 min. Ethyl acetate (100 ml) was added and the mixture poured into a separating funnel. The phases were separated and the aqueous phase was extracted with ethyl acetate (3×20 ml). The combined organic phases were washed with brine (20 ml), dried over anhydrous magnesium sulfate, filtered and concentrated affording an orange oil, which was purified by flash column chromatography (SiO2, ethyl acetate/petroleum ether, 45:55, v/v). The title product (1.42 g, 56%) was isolated as a colourless oil. m/z (ES+) 337 (M−H2O+H+); δH (CDCl3) 1.61-1.64(2H, m), 2.00-2.18(6H, m), 3.44(3H, s), 3.48(3H, s), 3.90-3.97(4H, m), 5.11(2H, s), 5.24(2H, s), 6.64(1H, dd), 6.82(1H, d), 7.20(1H, d).

Workup

  1. additionwas added
  2. stirringThe resulting solution was stirred at −78° C. for 1 hr
  3. temperatureto warm to room temperature overnight
  4. stirringthe reaction mixture stirred vigorously for 15 min
  5. additionthe mixture poured into a separating funnel
  6. customThe phases were separated
  7. extractionthe aqueous phase was extracted with ethyl acetate (3×20 ml)
  8. washThe combined organic phases were washed with brine (20 ml)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customaffording an orange oil, which
  13. customwas purified by flash column chromatography (SiO2, ethyl acetate/petroleum ether, 45:55

Sources & evidence

ORD record
ord-b22ea2569c434eb1ab8b68bc8c698756
Source dataset
uspto-grants-2004_09
Patent number
US06797731B2

Reaction notes

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