Diethyl Malonate → Diethyl 2-((1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)methyl)malonate

HRID 1855030Notes

Reaction equation

HRID 1855030 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].CC1C=CC(S(O[CH2:23][C:24]23[CH2:31][CH2:30][C:27]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([O:38][C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)[CH:33]=4)([CH2:28][CH2:29]2)[O:26][CH2:25]3)(=O)=O)=CC=1.[NH4+].[Cl-]>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-]>[O:38]([C:34]1[CH:33]=[C:32]([C:27]23[CH2:30][CH2:31][C:24]([CH2:23][CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])([CH2:29][CH2:28]2)[CH2:25][O:26]3)[CH:37]=[CH:36][CH:35]=1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 25517Ammonium ChlorideHCID 90408232(1-(3-Phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 90408709Diethyl 2-((1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)methyl)malonateYield 82%

Reagents, catalysts & solvents 1

HCID 67553Tetrabutylammonium IodideCatalyst

Procedure

Sodium (5 mg, 0.215 mmol) was dissolved in EtOH (2 mL) to form a solution of NaOEt and then diethyl malonate (0.033 mL, 0.215 mmol) was added. The reaction mixture was stirred at rt for 30 min and (1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)methyl 4-methylbenzenesulfonate (10 mg, 0.022 mmol) was then added. The reaction was stirred at 120° C. under microwave conditions for 30 min. Catalytic amount of n-Bu4NI was added and the reaction was stirred at 120° C. under microwave conditions for 18 h. The reaction was added sat′d aq NH4Cl and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude oil was purified by flash chromatography on SiO2 (0 to 50% EtOAc:hexanes) to afford the title compound (8 mg, 82% yield) as a clear oil. LCMS, [M-Et+H]+=425.4.

Workup

  1. stirringThe reaction was stirred at 120° C. under microwave conditions for 30 min
  2. stirringthe reaction was stirred at 120° C. under microwave conditions for 18 h
  3. additionThe reaction was added
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude oil was purified by flash chromatography on SiO2 (0 to 50% EtOAc:hexanes)

Sources & evidence

ORD record
ord-0ba90586334a4f0f98c315fff77a7a23
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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