2,2,5,5-Tetramethyltetrahydro-3-ketofuran → HCID 66823358, compound

HRID 879074Notes

Reaction equation

HRID 879074 reaction equation
[CH3:1][C:2]1([CH3:10])[C:6](=[O:7])[CH2:5][C:4]([CH3:9])([CH3:8])[O:3]1.C[O-].[Na+].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][C:24]([CH:27]3[CH2:29][CH2:28]3)=[C:23]([CH:30]=O)[CH:22]=2)=[C:17]([F:32])[CH:16]=1>COCCOC.C(OCC)C>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][C:24]([CH:27]3[CH2:28][CH2:29]3)=[C:23]([CH:30]=[C:5]3[C:4]([CH3:9])([CH3:8])[O:3][C:2]([CH3:10])([CH3:1])[C:6]3=[O:7])[CH:22]=2)=[C:17]([F:32])[CH:16]=1

Participants

6

Reactant 3

HCID 1385112,2,5,5-Tetramethyltetrahydro-3-ketofuranHCID 10942334Sodium MethoxideHCID 86663669HCID 86663669, compound

Product 1

HCID 66823358HCID 66823358, compoundYield 91,920%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To an ice-cold solution of dihydro-2,2,5,5-tetramethylfuran-3-one (8.40 g, 0.059 mol) in anhydrous 1,2-dimethoxyethane (75 ml) is added sodium methoxide (3.60 g, 0.066 mol) in one portion, and the mixture is stirred at this temperature for 30 minutes. A solution of 4′-chloro-4-cyclopropyl-2′-fluorobiphenyl-3-carbaldehyde (14.80 g, 0.054 mmol) is then added dropwise over 20 minutes, maintaining temperature below 10° C. The reaction mixture is stirred at this temperature for 1 hour, then allowed to warm to room temperature before diluting with diethyl ether and distilled water. The two phases are separated, and the aqueous phase is extracted again with diethyl ether (×2). Organic fractions are combined, washed with brine, then dried over magnesium sulfate. The suspension is filtered and the filtrate concentrated in vacuo to afford 4-[1-(4′-chloro-4-cyclopropyl-2′-fluorobiphenyl-3-yl)methylidene]-2,2,5,5-tetramethyldihydrofuran-3-one (19.80 g) which is of sufficient purity to use directly in the next step.

Workup

  1. temperaturemaintaining temperature below 10° C
  2. stirringThe reaction mixture is stirred at this temperature for 1 hour
  3. distillationdistilled water
  4. customThe two phases are separated
  5. extractionthe aqueous phase is extracted again with diethyl ether (×2)
  6. washwashed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationThe suspension is filtered
  9. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-dc11363d8d6946b19f9a1bc3a7231488
Source dataset
uspto-grants-2015_03
Patent number
US08987476B2

Reaction notes

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