Sodium hydride → HCID 11206816, compound

HRID 1716817Notes

Reaction equation

HRID 1716817 reaction equation
[C:1]1([C:7]([OH:12])([CH3:11])[C:8](=[O:10])[CH3:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.C[O:14][C:15](=[O:23])[C:16](OC)(OC)OC.[H-].[Na+]>C1COCC1>[C:1]1([C:7]2([CH3:11])[O:12][C:16]([C:15]([OH:23])=[O:14])=[CH:9][C:8]2=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 12586559Methyl 2,2,2-trimethoxyacetateHCID 16126017HCID 16126017, compound

Product 1

HCID 11206816HCID 11206816, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

To an oven-dried 10 mL vial was added 3-cyclohex-1-enyl-3-hydroxy-butan-2-one (0.80 g, 4.80 mmol), THF (4 mL) and trimethoxy-acetic acid methyl ester (0.94 g, 5.76 mmol). The vial was capped with a septum and flushed with Ar. In a dried round-bottom flask with stirring bar was added sodium hydride (60% dispersion in mineral oil, 0.57 g, 14.4 mmol) and THF (20 mL). The flask was capped with a septum and flushed with Ar. The contents of the vial were added dropwise via syringe to the round-bottom flask. The round-bottom flask was equipped with a condenser and septum and heated to 65° C. under Ar for 12 h. The reaction was quenched with sat'd NH4Cl (20 mL) and the layers were separated. The organic extract was concentrated and dissolved in 1,4-dioxane (4 mL). The solution was mixed with conc. HCl (0.5 mL) and stirred overnight at rt. Saturated NaHCO3 solution (20 mL) was added and the reaction was extracted with EtOAc (3×50 mL). The extracts were dried (Na2SO4), filtered and concentrated. The crude product was purified with a Biotage 25+M silica gel column using a gradient of 0-10% EtOAc in hexanes providing 0.37 g (32%) of racemic 5-cyclohex-1-enyl-5-methyl-4-oxo-4,5-dihydro-furan-2-carboxylic acid methyl ester: LC-MS) m/z 235 (M−1); 1H NMR (400 MHz, CDCl3) 6.20 (s, 1H), 5.90-5.88 (m, 1H), 3.96 (s, 3H), 2.14-2.04 (m, 3H), 1.87-1.78 (m, 1H), 1.63-1.52 (m, 4H), 1.54 (s, 3H).

Workup

  1. customThe vial was capped with a septum
  2. customflushed with Ar
  3. customThe flask was capped with a septum
  4. customflushed with Ar
  5. additionThe contents of the vial were added dropwise via syringe to the round-bottom flask
  6. customThe round-bottom flask was equipped with a condenser
  7. customThe reaction was quenched with sat'd NH4Cl (20 mL)
  8. customthe layers were separated
  9. extractionThe organic extract
  10. concentrationwas concentrated
  11. dissolutiondissolved in 1,4-dioxane (4 mL)
  12. additionThe solution was mixed with conc. HCl (0.5 mL)
  13. stirringstirred overnight at rt
  14. additionSaturated NaHCO3 solution (20 mL) was added
  15. extractionthe reaction was extracted with EtOAc (3×50 mL)
  16. dry with materialThe extracts were dried (Na2SO4)
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customThe crude product was purified with a Biotage 25+M silica gel column

Sources & evidence

ORD record
ord-babeb52795154236acd85e7f0affcbaf
Source dataset
uspto-grants-2010_09
Patent number
US07803837B2

Reaction notes

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