Tetrahydrofuran → HCID 66583106, compound

HRID 334363Notes

Reaction equation

HRID 334363 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6]2)OCC1.[Li+].CC([N-][CH:21]([CH3:23])[CH3:22])C.Cl[CH2:25][O:26][CH2:27]C1C=CC=CC=1.O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+].[CH2:61]1[CH2:65]OC[CH2:62]1>O>[CH2:25]([O:26][CH2:27][C:8]1([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6][C:5](=[O:1])[CH2:10][CH2:9]1)[C:22]1[CH:21]=[CH:23][CH:65]=[CH:61][CH:62]=1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 137983Benzyl chloromethyl etherHCID 180504Ceric ammonium nitrateHCID 2724682Lithium diisopropylamideHCID 10488810Ethyl 1,4-dioxaspiro(4.5)decane-8-carboxylate

Product 1

HCID 66583106HCID 66583106, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of ethyl 1,4-dioxaspiro[4.5]decane-8-carboxylate (7.89 g, 36.8 mmol) in THF (120 mL) was added LDA (1.5 eq) at −78° C. and stirred for 30 min. Then, benzyl chloromethyl ether (10.7 mL, 92.1 mmol) was added dropwise. The resulting mixture was slowly warmed to rt and stirred overnight. The reaction was quenched with H2O and combined with ammonium choloride. All the volatiles were removed. The residue was diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated. The resulting brownish oil was dissolved in CH3CN (150 mL) and a solution of CAN (2.02 g 3.68 mmol) in H2O (150 mL) was added. The resulting mixture was heated at 70° C. for 6 h. Organic solvent was removed under reduced pressure. The aqueous residue was extracted with EtOAc (*3) and the combined organic layers were washed brine, dried over Na2SO4 and concentrated. The crude product was purified by two SiO2 columns (firstly 0-30% EtOAc/Hexanes, then 50-100% DCM/Hexanes, Rf=0.2 in 20% EtOAc) to afford ethyl 1-(benzyloxymethyl)-4-oxocyclohexanecarboxylate as a pale yellow oil (5.72 g). HPLC-MS TR=2.08 min (UV 254 nm, 5 min method); mass calculated for formula C17H22O4 290.2, observed LCMS m/z 291.1 (M+H).

Workup

  1. stirringstirred overnight
  2. customThe reaction was quenched with H2O
  3. customAll the volatiles were removed
  4. additionThe residue was diluted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. dissolutionThe resulting brownish oil was dissolved in CH3CN (150 mL)
  9. temperatureThe resulting mixture was heated at 70° C. for 6 h
  10. customOrganic solvent was removed under reduced pressure
  11. extractionThe aqueous residue was extracted with EtOAc (*3)
  12. washthe combined organic layers were washed brine
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated
  15. customThe crude product was purified by two SiO2 columns (firstly 0-30% EtOAc/Hexanes

Sources & evidence

ORD record
ord-567de15e99464a13a4c3d7e5d4f6d826
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

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