Ethyl Acetate → 1-(4-(Trifluoromethoxy)phenyl)cyclobutanecarbaldehyde

HRID 1749147Notes

Reaction equation

HRID 1749147 reaction equation
[F:1][C:2]([F:17])([F:16])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:14]#N)[CH2:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.[H-].C([Al+]CC(C)C)C(C)C.C(OCC)(=[O:30])C>ClCCl>[F:1][C:2]([F:17])([F:16])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([CH:14]=[O:30])[CH2:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 21225700DiisobutylaluminumhydrideHCID 219020771-[4-(Trifluoromethoxy)phenyl]cyclobutanecarbonitrile

Product 1

HCID 871341821-(4-(Trifluoromethoxy)phenyl)cyclobutanecarbaldehydeYield 55.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 31A (4.82 g, 0.02 mol) in dry dichloromethane (100 mL) at −78° C. under an argon atmosphere was added diisobutylaluminum hydride (24 mL, 1M solution in toluene). The reaction mixture was stirred at the same temperature for 1 hour and then quenched by dropwise addition of potassium sodium tartrate (10% solution in water). The resulting mixture was warmed to room temperature, stirred vigorously for 40 minutes and then diluted with dichloromethane. The organic phase was separated and the aqueous phase extracted with dichloromethane. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and the solvent was evaporated under reduced pressure. The crude product was purified by silica gel column chromatography, eluted with 100% petroleum ether to petroleum ether: ethyl acetate=50:1 to 30:1) to give title compound as a viscous oil (2.7 g, yield 55.3%). LC-MS: m/z (M+H)+ 245.

Workup

  1. customquenched by dropwise addition of potassium sodium tartrate (10% solution in water)
  2. stirringstirred vigorously for 40 minutes
  3. additiondiluted with dichloromethane
  4. customThe organic phase was separated
  5. extractionthe aqueous phase extracted with dichloromethane
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customthe solvent was evaporated under reduced pressure
  10. customThe crude product was purified by silica gel column chromatography
  11. washeluted with 100% petroleum ether to petroleum ether

Sources & evidence

ORD record
ord-55ad090d08b54c6ba4e5f0bf11d8becc
Source dataset
uspto-grants-2015_10
Patent number
US09156788B2

Reaction notes

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