Water → HCID 58909942, compound

HRID 1296034Notes

Reaction equation

HRID 1296034 reaction equation
Br[C:2]1[CH:34]=[C:33]([C:35]([NH:37][CH3:38])=[O:36])[C:32]([O:39][CH2:40][CH3:41])=[CH:31][C:3]=1[CH2:4][N:5]([CH2:13][C:14]([C:16]1[CH:21]=[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:19]([OH:26])=[C:18]([C:27]([CH3:30])([CH3:29])[CH3:28])[CH:17]=1)=[O:15])[C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9].[C-:42]#[N:43].[Na+].C(OCC)(=O)C.O>C(#N)CC.[Cu](I)I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:42]([C:2]1[CH:34]=[C:33]([C:35]([NH:37][CH3:38])=[O:36])[C:32]([O:39][CH2:40][CH3:41])=[CH:31][C:3]=1[CH2:4][N:5]([CH2:13][C:14]([C:16]1[CH:21]=[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:19]([OH:26])=[C:18]([C:27]([CH3:30])([CH3:29])[CH3:28])[CH:17]=1)=[O:15])[C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])#[N:43]

Participants

8

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 8929Sodium CyanideHCID 58910006HCID 58910006, compound

Product 1

HCID 58909942HCID 58909942, compoundYield 31.8%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalyst2×HCID 178418397HCID 178418397, compoundCatalyst2×HCID 7854PropionitrileSolvent

Procedure

After dissolving the tert-butyl N-{2-bromo-5-ethoxy-4-[(methylamino)carbonyl]benzyl}-N-{2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-2-oxoethyl}carbamate (2.71 g) in propionitrile (11 ml), sodium cyanide (420 mg), copper iodide (163 mg) and tetrakis(triphenylphosphine)palladium (495 mg) were added under a nitrogen atmosphere and the mixture was heated to reflux for one hour. Additional copper iodide (170 mg) and tetrakis(triphenylphosphine)palladium (500 mg) were added and heating to reflux was continued for 4 hours. Ethyl acetate and water were added to the reaction mixture and the resultant mixture was filtered with celite. The filtrate was washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate and, after filtering off the insoluble portion, was concentrated. The residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate) to yield the title compound (788 mg) as a white solid.

Workup

  1. additionwere added under a nitrogen atmosphere
  2. temperaturethe mixture was heated
  3. temperatureto reflux for one hour
  4. temperatureheating
  5. temperatureto reflux
  6. filtrationthe resultant mixture was filtered with celite
  7. washThe filtrate was washed with water and brine
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. filtrationafter filtering off the insoluble portion
  10. concentrationwas concentrated
  11. customThe residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate)

Sources & evidence

ORD record
ord-ed9e283193284cd390f4d51aad2b6576
Source dataset
uspto-grants-2007_07
Patent number
US07244730B2

Reaction notes

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