Diethyl Malonate → 8-Oxabicyclo[3.2.1]octane-3,3-dicarboxylic acid diethyl ester

HRID 1872886Notes

Reaction equation

[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[H][H].S(C1C=CC(C)=CC=1)(O)(=O)=O.S(C1C=CC(C)=CC=1)(O)(=O)=O.O[CH2:39][C@H:40]1[CH2:44][CH2:43][C@@H:42]([CH2:45]O)[O:41]1>CN(C)C=O>[CH2:12]([O:11][C:3]([C:4]1([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:45][CH:42]2[O:41][CH:40]([CH2:44][CH2:43]2)[CH2:39]1)=[O:10])[CH3:13]

Participants

Conditions

Temperature: 140 °C

Procedure

Sodium hydride (2.28 grams, 95 mmole) was added in portions to a stirred solution of diethyl malonate (15 mL, 99 mmole) in N,N-dimethylformamide (400 mL). The mixture was stirred for 45 minutes at which time evolution of hydrogen was complete. A solution of cis-2,5-bis(hydroxymethyl)tetrahydrofuran ditosylate (19.0 grams, 43 mmole) in N,N-dimethylformamide (400 mL) was then added dropwise. The mixture was heated in an oil bath at 140° C. overnight. After cooling to room temperature, the mixture was quenched by addition of saturated aqueous ammonium chloride solution and concentrated under vacuum. The residual oil was taken up in water and extracted with diethyl ether. The organic extract was washed with water and brine, dried over magnesium sulfate and concentrated to an oil. Distillation under vacuum afforded the title compound (7.8 grams, 71%) as a clear oil.

Workup

temperatureAfter cooling to room temperature
customthe mixture was quenched by addition of saturated aqueous ammonium chloride solution
concentrationconcentrated under vacuum
extractionextracted with diethyl ether
extractionThe organic extract
washwas washed with water and brine
dry with materialdried over magnesium sulfate
concentrationconcentrated to an oil
distillationDistillation under vacuum

Sources & evidence

ORD record: ord-288cba4356fb43b0904f4bd120b6d0b5
Source dataset: uspto-grants-2000_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06110964

Reaction notes

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