4'-Isobutylacetophenone → 3-(4-Isobutylphenyl)but-2-enoic acid methyl ester

HRID 1500251

Reaction equation

HRID 1500251 reaction equation
[CH3:1][Si]([N-][Si](C)(C)C)(C)C.[Li+].C[C:12](P(OC)(O)=O)([C:14]([O-:16])=[O:15])C.[CH2:22]([C:26]1[CH:31]=[CH:30][C:29]([C:32](=O)[CH3:33])=[CH:28][CH:27]=1)[CH:23]([CH3:25])[CH3:24]>C1COCC1.[NH4+].[Cl-]>[CH3:1][O:16][C:14](=[O:15])[CH:12]=[C:32]([C:29]1[CH:30]=[CH:31][C:26]([CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:27][CH:28]=1)[CH3:33]

Participants

6

Reactant 3

HCID 932144'-IsobutylacetophenoneHCID 2733832Lithium HexamethyldisilazideHCID 53413272Trimethylphosphonoacetate

Product 1

HCID 668685823-(4-Isobutylphenyl)but-2-enoic acid methyl esterYield 89.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a chilled (0° C.) solution of lithium bis(trimethylsilyl)amide (1.0 M, 56 mL) was dropwise added a solution of trimethylphosphonoacetate, keeping the temperature below 10° C. The solution was then allowed to warm to room temperature and stirred for an additional five minutes after which a solution of p-isobutylacetophenone in THF (25 mL) was added in one portion. The solution was slowly heated to 65° C. and allowed to reflux for thirty hours. The solution was cooled to room temperature then diluted with a 10% NH4Cl solution (100 mL), and extracted with ethyl acetate (2×100 mL). The organic layers were combined and dried over MgSO4, filtered, and filtrate concentrated to a white solid which was recrystallized from hexane/ethyl acetate to give 5.93 grams of 3-(4-isobutylphenyl)but-2-enoic acid methyl ester intermediate (89.9% yield).

Workup

  1. customthe temperature below 10° C
  2. additionwas added in one portion
  3. temperatureThe solution was slowly heated to 65° C.
  4. temperatureto reflux for thirty hours
  5. temperatureThe solution was cooled to room temperature
  6. extractionextracted with ethyl acetate (2×100 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationfiltrate concentrated to a white solid which
  10. customwas recrystallized from hexane/ethyl acetate

Sources & evidence

ORD record
ord-df21f23897ab43888c6d721433713a89
Source dataset
uspto-grants-2015_12
Patent number
US09206143B2

Linked notes

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