p-Anisoyl chloride → HCID 68655269, compound

HRID 2363373Notes

Reaction equation

HRID 2363373 reaction equation
[C:1]([O:5][C:6]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13](=[O:28])[C:14]([NH:17][C:18]([O:20]CC1C=CC=CC=1)=O)([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.C(Cl)(=O)[C:39]1[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=1>CO.C(Cl)Cl.[Pd]>[C:1]([O:5][C:6]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13](=[O:28])[C:14]([NH:17][C:18](=[O:20])[C:39]1[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=1)([CH3:15])[CH3:16])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 3

HCID 7477p-Anisoyl chlorideHCID 81531DiisopropylethylamineHCID 14805851HCID 14805851, compound

Product 1

HCID 68655269HCID 68655269, compoundYield 65.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To solution of 49 (1.00 g, 2.56 mmol) in MeOH (20 ml) was added 10% Pd/C (200 mg) and the mixture was stirred under H2 for 2 hours. The mixture was filtered through a 0.45 μm PTFE filter and the solvent removed in vacuo to yield a colorless oil. This oil was dissolved in CH2Cl2 (25 mL) and DIEA (660 μl, 3.79 mmol) and p-anisoyl chloride (480 mg, 2.8 mmol) were added. The solution was stirred at room temperature under N2 for 18 hours. The solvent was removed in vacuo and the oil dissolved in EtOAc. The organic phase was washed with 0.5N NaHSO4 (2×), water, saturated NaHCO3 (2×) and brine. The organic phase was dried over Na2SO4, filtered and evaporated to give a white solid which was purified by flash column chromatography, eluting with CH2Cl2/MeOH (99/1 to 98/2%) to give the title compound as a white solid (655 mg, 65% yield). 1H-NMR (500 MHz, CDCl3) δ 1.47 (s, 9H), 1.68-2.24 (m, 5H), 1.80 (d, 6H), 3.55-3.68 (m, 1H), 3.72-3.93 (m, 1H), 3.84 (s, 3H), 4.43-4.55 (m, 1H), 6.90 (d, 2H), 7.60 (br s, 1H), 7.77 (d, 2H) Analytical HPLC (C18 column) 8.98 min.

Workup

  1. filtrationThe mixture was filtered through a 0.45 μm PTFE
  2. filtrationfilter
  3. customthe solvent removed in vacuo
  4. customto yield a colorless oil
  5. stirringThe solution was stirred at room temperature under N2 for 18 hours
  6. customThe solvent was removed in vacuo
  7. dissolutionthe oil dissolved in EtOAc
  8. washThe organic phase was washed with 0.5N NaHSO4 (2×), water, saturated NaHCO3 (2×) and brine
  9. dry with materialThe organic phase was dried over Na2SO4
  10. filtrationfiltered
  11. customevaporated
  12. customto give a white solid which
  13. customwas purified by flash column chromatography
  14. washeluting with CH2Cl2/MeOH (99/1 to 98/2%)

Sources & evidence

ORD record
ord-c4956ec4d6274fa3aec87e55a5ae802f
Source dataset
uspto-grants-2014_04
Patent number
US08691848B2

Reaction notes

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