Methanol → Ethyl 3-(4-fluorophenyl)hexenoate

HRID 1954923Notes

Reaction equation

HRID 1954923 reaction equation
C([Li])CCC.C[OH:7].[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=O)[CH2:16][CH2:17][CH3:18])=[CH:11][CH:10]=1.[O:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1>>[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([CH2:16][CH2:17][CH3:18])=[CH:22][C:21]([O:20][CH2:24][CH3:23])=[O:7])=[CH:11][CH:10]=1

Participants

5

Reactant 4

HCID 887MethanolHCID 8028Tetrahydrofuran2×HCID 684984'-FluorobutyrophenoneHCID 178418339Butyllithium

Product 1

HCID 54012085Ethyl 3-(4-fluorophenyl)hexenoateYield 60%

Procedure

A solution of butyllithium, 2.5M in hexanes (166 ml, 0.416 mol, Aldrich) was added dropwise over 0.5 hr, with rapid mechanical stirring, to a solution of triethyl phosphonoacetate (93.2 g, 0.416 mol, Aldrich) in tetrahydrofuran (700 ml, anhydrous, Aldrich) at <5° C. while blanketed with a nitrogen atmosphere. This solution was stirred for an additional 0.25 hr and cooled to -5° C. with a methanol:ice bath and a solution of 4'-fluorobutyrophenone (69 g, 0.416 mol, Aldrich) in tetrahydrofuran (150 ml) was then added in one portion. Stirring was continued for 18 hr without additional cooling. The solution was concentrated to a dark camel sludge by spin evaporation in vacuo and diluted to 600 ml with deionized water. The aqueous solution was extracted with dichloromethane (5×500 ml) and the dichloromethane was concentrated by spin evaporation in vacuo. Distillation at reduced pressure gave 58.5 g (60%) of ethyl 3-(4-fluorophenyl)hexenoate as a mixture of (E) and (Z) isomers (ratio 1:1) as clear liquid b.p. 140-150° C. at aspirator pressure:

Workup

  1. stirringStirring
  2. waitwas continued for 18 hr without additional cooling
  3. concentrationThe solution was concentrated to a dark camel sludge by spin evaporation in vacuo
  4. additiondiluted to 600 ml with deionized water
  5. extractionThe aqueous solution was extracted with dichloromethane (5×500 ml)
  6. concentrationthe dichloromethane was concentrated by spin evaporation in vacuo
  7. distillationDistillation at reduced pressure

Sources & evidence

ORD record
ord-323a1f19e7234a90a2f340c9765cb76b
Source dataset
uspto-grants-2000_09
Patent number
US06124284

Reaction notes

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