Citric Acid → 8-(2-(Benzyloxy)ethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile

HRID 2193079Notes

Reaction equation

HRID 2193079 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[O:19]1[C:23]2([CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25][CH2:24]2)[O:22][CH2:21][CH2:20]1.Br[CH2:32][CH2:33][O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(OCC)(=O)C.O1CCCC1>[CH2:35]([O:34][CH2:33][CH2:32][C:26]1([C:29]#[N:30])[CH2:27][CH2:28][C:23]2([O:22][CH2:21][CH2:20][O:19]2)[CH2:24][CH2:25]1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 7912DiisopropylamineHCID 73833Benzene, ((2-bromoethoxy)methyl)-HCID 111164331,4-Dioxaspiro[4.5]decane-8-carbonitrileHCID 178418244HCID 178418244, compound

Product 1

HCID 675392928-(2-(Benzyloxy)ethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To 8 mL of a tetrahydrofuran solution containing 0.94 mL of diisopropylamine, 4.5 mL of 1.6 mol/L butyllithium/hexane was added dropwise at −78° C., the mixture was stirred at the same temperature for 1 hour, and then thereto was added dropwise 7 mL of a tetrahydrofuran solution containing 0.60 g of 1,4-dioxaspiro[4.5]decane-8-carbonitrile. After stirring at −78° C. for 1 hour, the mixture was added dropwise with 0.85 mL of benzyl 2-bromoethyl ether, and further stirred for 1 hour. The temperature of the reaction mixture was increased to room temperature, and then a 10% aqueous citric acid solution and ethyl acetate were added thereto. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with an aqueous saturated sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=6:1] to obtain 1.1 g of a colorless oily substance, 8-(2-(benzyloxy)ethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile.

Workup

  1. additionwas added dropwise at −78° C.
  2. stirringAfter stirring at −78° C. for 1 hour
  3. stirringfurther stirred for 1 hour
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washthe resultant solution was washed with an aqueous saturated sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe residue thus obtained
  10. customwas purified by silica gel column chromatography [eluent; hexane:ethyl acetate=6:1]

Sources & evidence

ORD record
ord-1ecdf4135bb6451f91d0e8e84c3e365b
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Reaction notes

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