Water → 1-Phenylcyclobutane-1-carbaldehyde

HRID 1266415Notes

Reaction equation

HRID 1266415 reaction equation
[C:1]1([C:7]2([C:11]#N)[CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].C([Al+]CC(C)C)C(C)C.C(OCC)(=[O:25])C.O>C1(C)C=CC=CC=1>[C:1]1([C:7]2([CH:11]=[O:25])[CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl Acetate2×HCID 844001-PhenylcyclobutanecarbonitrileHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 122261071-Phenylcyclobutane-1-carbaldehyde

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

10 g of 1-phenyl-cyclobutanecarbonitrile, dissolved in 70 ml of toluene, is mixed with 56 ml of diisobutylaluminum hydride in toluene (1.2 molar) at −72 to −69° C. After 4 hours at −75° C., 30 ml of ethyl acetate is added in drops. After heating to room temperature, additional ethyl acetate and water are added. It is filtered on diatomaceous earth, the organic phase is separated, dried (Na2SO4) and concentrated by evaporation. After chromatography on silica gel (hexane with 0-10% ethyl acetate), 7.6 g of 1-phenyl-cyclobutanecarbalde-hyde is obtained. 3 g of it is dissolved in 10 ml of tetrahydrofuran and added in drops at 0° C. to a solution, in which previously 5 g of triethyl-2-ethoxyphosphonoacetate in 70 ml of tetrahydrofuran was mixed at 0° C. with 10.3 ml of a 2 molar solution of lithium diisopropylamide in tetrahydro-furan/heptane/ethylbenzene. After 20 hours at room tempera-ture, water is added, it is extracted with ethyl acetate, dried (Na2SO4) and concentrated by evaporation. 2 g of this crude product is saponified with 28 ml of 1N sodium hydroxide solution. 1.32 g of the acid, which is heated for 20 hours to 90° C. with 25 ml of 1 molar sulfuric acid while being stirred vigorously, is obtained. After extraction with ether, drying (Na2SO4) and concentration by evaporation, 0.89 g of 3-(1-phenyl-cyclobutyl)-2-oxo-propionic acid is obtained as a yellowish oil.

Workup

  1. filtrationIt is filtered on diatomaceous earth
  2. customthe organic phase is separated
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-96b24fc359cd4459a82274b12d6e88ad
Source dataset
uspto-grants-2003_04
Patent number
US06548534B2

Reaction notes

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