Hydrochloric Acid → Ammonia

HRID 1433282Notes

Reaction equation

HRID 1433282 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[C:21]([C@@H:33]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH2:34][CH2:35][N:36]([CH:40]([CH3:42])[CH3:41])[CH:37]([CH3:39])[CH3:38])[CH:20]=2)=[CH:12][CH:11]=1)(C)(C)C.Cl.[CH2:51]([O:58][C:59]1[CH:64]=[CH:63][C:62]([C@@H:65]([O:68][Si:69]([C:72]([CH3:75])([CH3:74])[CH3:73])([CH3:71])[CH3:70])[CH2:66]Br)=[CH:61][C:60]=1[CH2:76][OH:77])[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1.C(=O)([O-])O.[Na+]>O1CCOCC1.O.C(OCC)(=O)C>[NH3:7].[CH2:51]([O:58][C:59]1[CH:64]=[CH:63][C:62]([C@@H:65]([O:68][Si:69]([C:72]([CH3:75])([CH3:74])[CH3:73])([CH3:71])[CH3:70])[CH2:66][NH:7][CH2:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)=[C:21]([C@@H:33]([C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[CH2:34][CH2:35][N:36]([CH:37]([CH3:39])[CH3:38])[CH:40]([CH3:42])[CH3:41])[CH:20]=3)=[CH:14][CH:15]=2)=[CH:61][C:60]=1[CH2:76][OH:77])[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 12988834[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanolHCID 57933204tert-butyl {2-[4-(2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethoxy)phenyl]ethyl}carbamate

Product 2

HCID 222AmmoniaHCID 57933171{2-(benzyloxy)-5-[(1R)-2-({2-[4-(2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethoxy)phenyl]ethyl}amino)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-butyl{2-[4-(2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethoxy)phenyl]ethyl}carbamate (Preparation 41, 830 mg, 1.25 mmol) was treated with hydrochloric acid (8 ml of a 4M solution in 1,4-dioxane) and stirred at room temperature overnight, and the solvent was removed in vacuo. The residue was dissolved in acteonitrile (8 ml) and {2-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanol (Sali patent, 560 mg, 1.24 mmol) and sodium hydrogen carbonate (368 mg, 4.34 mmol) added. Mixture heated to 85° C. and stirred overnight. Reaction was cooled to room temperature and ethyl acetate and water added, the aqueous layer was separated and washed with ethyl acetate and the combined organics dried (magnesium sulphate) and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (92.517.511 by volume) to furnish the title compound as a gum, 280 mg.

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in acteonitrile (8 ml)
  3. temperatureMixture heated to 85° C.
  4. stirringstirred overnight
  5. customReaction
  6. temperaturewas cooled to room temperature
  7. customthe aqueous layer was separated
  8. washwashed with ethyl acetate
  9. dry with materialthe combined organics dried (magnesium sulphate)
  10. customthe solvent removed in vacuo
  11. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-53c0b75beba049ccb718e3d771d60a80
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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