Acetic Acid → t-Butyl 2-oxo-4-(4-methylphenyl)-butanoate

HRID 1584083Notes

Reaction equation

HRID 1584083 reaction equation
[CH3:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.C(O)(=O)C.N1CCCCC1.[C:20]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])(=[O:24])[C:21]([CH3:23])=[O:22]>C1C=CC=CC=1.C(OCC)(=O)C.O>[O:22]=[C:21]([CH2:23][CH2:6][C:5]1[CH:8]=[CH:9][C:2]([CH3:1])=[CH:3][CH:4]=1)[C:20]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 77254-MethylbenzaldehydeHCID 8082PiperidineHCID 11309579t-butyl pyruvate

Product 1

HCID 12065883t-Butyl 2-oxo-4-(4-methylphenyl)-butanoate

Reagents, catalysts & solvents 3

HCID 241BenzeneSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-methylbenzaldehyde (2.5 mL, 21.2 mmol) in 25 mL of benzene was added 1 mL each of acetic acid and piperidine. The mixture was heated to reflux with azeotropic removal of water via a Dean-Stark trap. A solution of t-butyl pyruvate (3.36 g, 23.32 mmol) in 5 mL of benzene was added over 7 h by syringe pump. The mixture was cooled, diluted with ethyl acetate and washed three times with saturated aqueous sodium bicarbonate and three times with 1N hydrochloric acid. The organics were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by MPLC on silica-gel eluting with 2.5% ethyl acetate in hexane to give the desired product as a yellow oil: 1H NMR (200 MHz, CDCl3) δ7.75 (d, 1H, J=16.19 Hz), 7.49 (d, 2H, J=8.25 Hz), 7.24 (m, 3H), 2.37 (s, 3H), 1.58 (s, 9H). The above product was dissolved in ethyl acetate and held under hydrogen in the presence of 100 mg of 10% palladium on carbon for 2 hours. The mixture was filtered and concentrated in vacuo to give 1.196 g of the title compound as a pale-yellow oil: 1H NMR (200 MHz, CDCl3) δ7.1-6.9 (m, 4H), 3.12 (t, 2H, J=6.8 Hz), 2.90 (t, 2H, J=7.3 Hz), 1.56 (s, 9H). ##STR29## N-[1(R)-Benzyloxycarbonyl-5-(1,3-dioxo-isoindolin-2-yl)pentyl]-α-(S)-(2-phenyl-ethyl)!glycine-(L)-leucine, N-phenylamide (5d')

Workup

  1. temperatureThe mixture was heated
  2. temperatureThe mixture was cooled
  3. washwashed three times with saturated aqueous sodium bicarbonate and three times with 1N hydrochloric acid
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by MPLC on silica-gel
  8. washeluting with 2.5% ethyl acetate in hexane

Sources & evidence

ORD record
ord-76355f366bbe47dfb1a9a3fdaf36a8c6
Source dataset
uspto-grants-1999_08
Patent number
US05932551

Reaction notes

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