HCID 86653783, compound → HCID 67159766, compound

HRID 1021211Notes

Reaction equation

HRID 1021211 reaction equation
C([O:8][C:9]1[C:14]([CH3:15])=[C:13]([CH3:16])[C:12]([O:17]CC2C=CC=CC=2)=[C:11]([CH3:25])[C:10]=1[CH2:26][CH2:27][CH2:28][C:29]([NH:31][CH2:32][CH2:33][CH3:34])=[O:30])C1C=CC=CC=1>C(O)(C(F)(F)F)=O.[Pd]>[CH2:32]([NH:31][C:29](=[O:30])[CH2:28][CH2:27][CH2:26][C:10]1[C:9](=[O:8])[C:14]([CH3:15])=[C:13]([CH3:16])[C:12](=[O:17])[C:11]=1[CH3:25])[CH2:33][CH3:34]

Participants

4

Reactant 1

HCID 86653783HCID 86653783, compound

Product 1

HCID 67159766HCID 67159766, compoundYield 73.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
40 °C

Procedure

A stirred solution of 4-(2,5-bis(benzyloxy)-3,4,6-trimethylphenyl)-N-propylbutanamide (176.6 mg) in TFA (2 mL) was treated with Pd/C (40 mg, 5% Pd by wt), sparged with H2 and heated to 40° C. for 2.25 h. The reaction was cooled, diluted with CH2Cl2, (4 mL) filtered and the solids washed 2×3 mL CH2Cl2 before concentration to a brown oil which solidified upon standing. The crude hydroquinone was dissolved into 1 mL MeCN and 1.5 mL 1 M aqueous CAN added (1.5 mmol, 3.9 equiv.). After 0.25 h, 5 mL EtOAc was added and the organics washed with 4×3 mL saturated NaCl (aq). The combined aqueous layers were back-extracted 2×3 mL EtOAc, the combined organics dried over Na2SO4, concentrated and purified by flash chromatography (gradient elution, 10-50% EtOAc/heptane) yielding N-propyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide as a yellow solid (78.0 mg), MS M++H 278; 1H NMR (400 MHz, CDCl3) δ=5.83 (m, 1 H), 3.24 (q, 2 H), 2.50 (t, 2 H), 2.22 (t, 2 H), 2.08 (s, 3H), 1.97 (s, 6H), 1.71 (pent, 2 H), 1.54 (m, 2 H), 0.92 (t, 3 H) ppm.

Workup

  1. customsparged with H2
  2. temperatureThe reaction was cooled
  3. additiondiluted with CH2Cl2, (4 mL)
  4. filtrationfiltered
  5. washthe solids washed 2×3 mL CH2Cl2
  6. concentrationbefore concentration to a brown oil which
  7. dissolutionThe crude hydroquinone was dissolved into 1 mL MeCN and 1.5 mL 1 M aqueous CAN
  8. additionadded (1.5 mmol, 3.9 equiv.)
  9. addition5 mL EtOAc was added
  10. washthe organics washed with 4×3 mL saturated NaCl (aq)
  11. extractionThe combined aqueous layers were back-extracted 2×3 mL EtOAc
  12. dry with materialthe combined organics dried over Na2SO4
  13. concentrationconcentrated
  14. custompurified by flash chromatography (gradient elution, 10-50% EtOAc/heptane)

Sources & evidence

ORD record
ord-7191515a779549649ab23803b12758c0
Source dataset
uspto-grants-2014_05
Patent number
US08716527B2

Reaction notes

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