Methoxymethyl-triphenylphosphonium chloride → HCID 86638535, compound

HRID 885208Notes

Reaction equation

HRID 885208 reaction equation
[Cl-].[CH3:2][O:3]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[K+].[F:30][C:31]1[CH:32]=[C:33]([C:38]2([CH:41]=O)[CH2:40][CH2:39]2)[CH:34]=[C:35]([F:37])[CH:36]=1>O1CCCC1>[F:37][C:35]1[CH:34]=[C:33]([C:38]2([CH2:41][CH:2]=[O:3])[CH2:39][CH2:40]2)[CH:32]=[C:31]([F:30])[CH:36]=1

Participants

5

Reactant 3

HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 23665647Potassium tert-butoxideHCID 83808383HCID 83808383, compound

Product 1

HCID 86638535HCID 86638535, compoundYield 37.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred, cooled (0° C.) solution of (methoxymethyl)triphenylphosphonium chloride (24.9 g) in tetrahydrofuran (190 ml) under an argon atmosphere was added slowly a solution of potassium tert.butoxide in tetrahydrofuran (30 ml) followed (after 30 min stirring) by a solution of 1-(3,5-difluoro-phenyl)-cyclopropanecarbaldehyde (6.3 g) in tetrahydrofuran (40 ml). Stirring was continued overnight, then the reaction mixture was quenched by adding an aqueous sodium chloride solution. The mixture was extracted with ethyl acetate twice and the combined organic layers were dried over MgSO4 and concentrated. The crude enol ether was dissolved in acetone (20 ml) and stirred with 6 M aqueous hydrochloric acid (40 ml) for 6 hours at room temperature. Ethyl acetate was added, the organic layer was separated, washed with brine, dried over MgSO4 and concentrated. The residue was purified by column chromatography (SiO2; heptane/EtOAc=4:1) to give [1-(3,5-difluoro-phenyl)-cyclopropyl]-acetaldehyde as yellow liquid (2.55 g). 1H-NMR (300 MHz, CDCl3, δ): 0.92-0.98 (m, 2H), 1.00-1.06 (m, 2H), 2.65 (d, J=2 Hz, 2H), 6.60-6.67 (m, 1H), 6.75-6.81 (m, 2H), 9.74 (t, J=2 Hz, 1H).

Workup

  1. customthe reaction mixture was quenched
  2. additionby adding an aqueous sodium chloride solution
  3. extractionThe mixture was extracted with ethyl acetate twice
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe crude enol ether was dissolved in acetone (20 ml)
  7. stirringstirred with 6 M aqueous hydrochloric acid (40 ml) for 6 hours at room temperature
  8. additionEthyl acetate was added
  9. customthe organic layer was separated
  10. washwashed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated
  13. customThe residue was purified by column chromatography (SiO2; heptane/EtOAc=4:1)

Sources & evidence

ORD record
ord-889e5000bb344c22919f15476f78ccb4
Source dataset
uspto-grants-2012_08
Patent number
US08242153B2

Reaction notes

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