Methyl iodide → 64776-06-3

HRID 866394Notes

Reaction equation

HRID 866394 reaction equation
[H-].[Na+].[CH2:3]1[C:6]2([CH2:9][CH2:8][CH2:7]2)[CH2:5][CH:4]1[C:10]([OH:12])=[O:11].[CH:13]([N-]C(C)C)(C)C.[Li+].CI>C1COCC1>[CH3:13][C:4]1([C:10]([OH:12])=[O:11])[CH2:5][C:6]2([CH2:9][CH2:8][CH2:7]2)[CH2:3]1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 2724682Lithium diisopropylamideHCID 20320775Spiro[3.3]heptane-2-carboxylic acid

Product 1

HCID 2032077764776-06-3Yield 82.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

A slurry of 2.15 g (44.2 mmol) of sodium hydride (50% in oil) in 45.0 ml of dry THF was stirred under argon at -20° C. A solution of 5.52 g (40.0 mmol) of spiro[3.3]heptane-2-carboxylic acid in 5.0 ml of dry THF was added dropwise. The reaction mixture was stirred for 0.5 hr at -20° C. A solution of 44.5 mmol of freshly-prepared, -20° C lithium diisopropylamide in 31.0 ml of THF was added to the reaction mixture. The reaction mixture was stirred for 0.3 hr at 0° C. Methyl iodide (2.80 ml, 44.5 mmol) was added, and the reaction mixture stirred an additional 2.0 hr at 25° C. The reaction mixture was cooled to -20° C and the reaction quenched by careful addition of cold 10% aqueous HCl. The mixture was extracted with 1:1 ethylacetate-ether. The extracts were washed with brine, then dried (MgSO4), filtered, and solvents evaporated in vacuo. The residue was dissolved in 1 N NaOH and extacted three times with ether. The aqueous layer was acidified with 6 N HCl and extracted with 1:1 ethyl-acetate-ether. These extracts were washed with brine, dried (MgSO4), filtered and evaporated in vacuo to yield 5.1 g of 2-methylspiro[3.3]heptane-2-carboxylic acid as a light yellow oil (82.5%).

Workup

  1. additionwas added to the reaction mixture
  2. stirringThe reaction mixture was stirred for 0.3 hr at 0° C
  3. stirringthe reaction mixture stirred an additional 2.0 hr at 25° C
  4. temperatureThe reaction mixture was cooled to -20° C
  5. customthe reaction quenched by careful addition of cold 10% aqueous HCl
  6. extractionThe mixture was extracted with 1:1 ethylacetate-ether
  7. washThe extracts were washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customsolvents evaporated in vacuo
  11. dissolutionThe residue was dissolved in 1 N NaOH
  12. extractionextracted with 1:1 ethyl-acetate-ether
  13. washThese extracts were washed with brine
  14. dry with materialdried (MgSO4)
  15. filtrationfiltered
  16. customevaporated in vacuo

Sources & evidence

ORD record
ord-2e77a0be6452465ab4a783dedb0f2415
Source dataset
uspto-grants-1978_07
Patent number
US04098823

Reaction notes

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