Ethyl diazoacetate → 2-Methoxymethyl-2,6,6-trimethyl-3,5-dioxotetrahydropyran-4-carboxylic acid ethyl ester

HRID 1191580Notes

Reaction equation

HRID 1191580 reaction equation
[CH3:1][O:2][CH2:3][C:4]1([CH3:13])[C:8](=[O:9])[C:7](=[O:10])[C:6]([CH3:12])([CH3:11])[O:5]1.[N+](=[CH:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N-]>COC(C)(C)C.[Cl-].[Zn+2].[Cl-]>[CH2:20]([O:19][C:17]([CH:16]1[C:7](=[O:10])[C:6]([CH3:11])([CH3:12])[O:5][C:4]([CH2:3][O:2][CH3:1])([CH3:13])[C:8]1=[O:9])=[O:18])[CH3:21]

Participants

5

Reactant 2

HCID 12192Ethyl diazoacetateHCID 594459142-Methoxymethyl-2,5,5-trimethylfuran-3,4-dione

Product 1

HCID 684865432-Methoxymethyl-2,6,6-trimethyl-3,5-dioxotetrahydropyran-4-carboxylic acid ethyl esterYield 67%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 15413tert-Butyl methyl etherSolvent3×

Procedure

To a solution of zinc chloride (11.80 ml, 11.80 mmol, 1M solution in diethyl ether) at 8° C. is carefully added a second solution of 2-methoxymethyl-2,5,5-trimethylfuran-3,4-dione (2.15 g, 11.56 mmol) in tert-butyl methyl ether (8 ml). This mixture is allowed to warm to 15° C. at which stage a solution of ethyl diazoacetate (1.35 g, 11.84 mmol) in tert-butyl methyl ether (6 ml) is added dropwise over 1 hour, maintaining an internal temperature below 21° C. with further stirring at room temperature overnight. The mixture is diluted with tert-butyl methyl ether (15 ml), washed with 1M hydrochloric acid (3×20 ml) and extracted with 1M sodium hydroxide (2×100 ml). To this aqueous phase is added solid sodium chloride, followed by acidification with concentrated hydrochloric acid then the mixture is extracted with dichloromethane. The organic extract is dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated in vacuo to afford 2-methoxymethyl-2,6,6-trimethyl-3,5-dioxo-tetrahydropyran-4-carboxylic acid ethyl ester (2.11 g) as a pink oil.

Workup

  1. additionis added dropwise over 1 hour
  2. temperaturemaintaining an internal temperature below 21° C.
  3. washwashed with 1M hydrochloric acid (3×20 ml)
  4. extractionextracted with 1M sodium hydroxide (2×100 ml)
  5. additionTo this aqueous phase is added solid sodium chloride
  6. extractionthe mixture is extracted with dichloromethane
  7. extractionThe organic extract
  8. dry with materialis dried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate is concentrated in vacuo

Sources & evidence

ORD record
ord-bf176b65950f4aa1aad7049d61b4852e
Source dataset
uspto-grants-2014_03
Patent number
US08680012B2

Reaction notes

Loading…