Ammonium formate → 5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}amino)ethyl]benzene-1,3-diol

HRID 1433269Notes

Reaction equation

HRID 1433269 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]([C@@H:23]([O:62][Si:63]([C:66]([CH3:69])([CH3:68])[CH3:67])([CH3:65])[CH3:64])[CH2:24][NH:25][CH2:26][CH2:27][C:28]2[CH:61]=[CH:60][C:31]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([OH:43])=[C:39]([C@@H:44]([C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[CH2:45][CH2:46][N:47]([CH:51]([CH3:53])[CH3:52])[CH:48]([CH3:50])[CH3:49])[CH:38]=3)=[CH:30][CH:29]=2)[CH:12]=[C:13]([O:15]CC2C=CC=CC=2)[CH:14]=1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.[OH-].[OH-].[Pd+2]>[Si:63]([O:62][C@H:23]([C:11]1[CH:12]=[C:13]([OH:15])[CH:14]=[C:9]([OH:8])[CH:10]=1)[CH2:24][NH:25][CH2:26][CH2:27][C:28]1[CH:61]=[CH:60][C:31]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]2[CH:42]=[CH:41][C:40]([OH:43])=[C:39]([C@@H:44]([C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=3)[CH2:45][CH2:46][N:47]([CH:48]([CH3:50])[CH3:49])[CH:51]([CH3:53])[CH3:52])[CH:38]=2)=[CH:30][CH:29]=1)([C:66]([CH3:69])([CH3:67])[CH3:68])([CH3:65])[CH3:64]

Participants

5

Reactant 2

HCID 2723923Ammonium formate3×HCID 579332204-(4-[4-(2-{[(2R)-2-[3,5-bis(benzyloxy)phenyl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl]amino}ethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol

Product 1

HCID 579331775-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}amino)ethyl]benzene-1,3-diol

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalyst3×HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

4-{4-[4-(2-{[(2R)-2-[3,5-bis(benzyloxy)phenyl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl]amino}ethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol (Preparation 33, 720 mg, 0.76 mmol), ammonium formate (960 mg, 15.0 mmol) and 20% palladium hydroxide on carbon (110 mg) were mixed in methanol (8 ml) and stirred at 70° C. for 1 hour under nitrogen. Further ammonium formate (300 mg, 4.75 mmol) and 20% palladium hydroxide on carbon (30 mg) were then added and heating continued at 70° C. for further 1 hour. Reaction mixture was then cooled and filtered, the filtrate was collected and the solvent removed in vacuo. The residue was dissolved in methanol (8 ml) and ammonium formate (900 mg, 14 mmol) and 20% palladium hydroxide on carbon (100 mg) were added and stirred at 70° C. for 1 hour under nitrogen. Reaction mixture was then cooled and filtered, the filtrate was collected and the solvent removed in vacuo. The residue was dissolved in ethyl actate (25 ml) and saturated aqueous sodium hydrogen carbonate (25 ml). Organics were separated and washed with brine (15 ml), dried (magnesium sulphate) and solvent was removed in vacuo to furnish the title compound as an off-white foam, 555 mg.

Workup

  1. temperatureheating
  2. waitcontinued at 70° C. for further 1 hour
  3. customReaction mixture
  4. temperaturewas then cooled
  5. filtrationfiltered
  6. customthe filtrate was collected
  7. customthe solvent removed in vacuo
  8. dissolutionThe residue was dissolved in methanol (8 ml)
  9. stirringstirred at 70° C. for 1 hour under nitrogen
  10. customReaction mixture
  11. temperaturewas then cooled
  12. filtrationfiltered
  13. customthe filtrate was collected
  14. customthe solvent removed in vacuo
  15. dissolutionThe residue was dissolved in ethyl actate (25 ml)
  16. customOrganics were separated
  17. washwashed with brine (15 ml)
  18. dry with materialdried (magnesium sulphate) and solvent
  19. customwas removed in vacuo

Sources & evidence

ORD record
ord-37fdfd228f444e59b09ea530bbac43ad
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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