Sodium hydride → (3Z)-3-(4,4-dimethyl-2-oxopentylidene)spiro[bicyclo[2.2.1]heptane-7,1'-cyclopropan]-2-one

HRID 1888880Notes

Reaction equation

HRID 1888880 reaction equation
COP([CH2:7][C:8](=[O:14])[CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])(=O)OC.[H-].[Na+].[C:17]12([CH:23]3[CH2:24][CH2:25][CH:20]1[C:21](=[O:27])[C:22]3=O)[CH2:19][CH2:18]2>C1COCC1>[CH3:11][C:10]([CH3:13])([CH3:12])[CH2:9][C:8](=[O:14])/[CH:7]=[C:22]1/[C:21](=[O:27])[CH:20]2[C:17]3([CH2:18][CH2:19]3)[CH:23]/1[CH2:24][CH2:25]2.[CH3:11][C:10]([CH3:13])([CH3:12])[CH2:9][C:8](=[O:14])/[CH:7]=[C:22]1\[C:21](=[O:27])[CH:20]2[C:17]3([CH2:18][CH2:19]3)[CH:23]\1[CH2:24][CH2:25]2

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 144441Spiro[bicyclo[2.2.1]heptane-7,1'-cyclopropane]-2,3-dioneHCID 25112585(4,4-Dimethyl-2-oxo-pentyl)-phosphonic acid dimethyl ester

Product 2

HCID 68537264(3Z)-3-(4,4-dimethyl-2-oxopentylidene)spiro[bicyclo[2.2.1]heptane-7,1'-cyclopropan]-2-oneHCID 68541247(3E)-3-(4,4-dimethyl-2-oxopentylidene)spiro[bicyclo[2.2.1]heptane-7,1'-cyclopropan]-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution (4,4-dimethyl-2-oxo-pentyl)-phosphonic acid dimethyl ester (1.249 g) in THF (40 ml) was cooled to 0° C. under an argon atmosphere and sodium hydride (0.268 g) was added in 4 portions. Spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dione (1.023 g) dissolved in THF (30 ml) was then added dropwise to the reaction mixture. The mixture was then stirred for further 15 minutes at 0° C. (until completion of reaction according to TLC analysis). The reaction mixture was partitioned between water/3N HCl and AcOEt, the layers were separated, the organic layer washed with saturated, aqueous NaCl, dried over Na2SO4, filtered and evaporated. The residue was purified by flash chromatography with heptane/AcOEt: 100% to 95% as eluant to give (3E)-3-(4,4-dimethyl-2-oxopentylidene)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropan]-2-one (0.284 g) and (3Z)-3-(4,4-dimethyl-2-oxopentylidene)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropan]-2-one (0.287 g) as yellow oils, respectively, that were directly used in the next step. Assignment of the E/Z isomers was done by NMR.

Workup

  1. additionwas then added dropwise to the reaction mixture
  2. custom(until completion of reaction according to TLC analysis)
  3. customThe reaction mixture was partitioned between water/3N HCl and AcOEt
  4. customthe layers were separated
  5. washthe organic layer washed with saturated, aqueous NaCl
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash chromatography with heptane/AcOEt

Sources & evidence

ORD record
ord-911be6a1b2504d639609e89e6c5f6592
Source dataset
uspto-grants-2013_08
Patent number
US08501940B2

Reaction notes

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