[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanol → Ammonia

HRID 1433292Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1433292
Cl.Cl.C([N:7](CCC1C=CC(OCCCCC2C=CC(O)=C([C@@H](C3C=CC=CC=3)CCN(C(C)C)C(C)C)C=2)=CC=1)C([O:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][NH2:30])=[CH:24][CH:23]=2)=[CH:13][C:12]=1[C@@H:31]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:32][CH2:33][N:34]([CH:38]([CH3:40])[CH3:39])[CH:35]([CH3:37])[CH3:36])=O)(C)(C)C.[CH2:83]([O:90][C:91]1[CH:96]=[CH:95][C:94]([C@@H:97]([O:100][Si:101]([C:104]([CH3:107])([CH3:106])[CH3:105])([CH3:103])[CH3:102])[CH2:98]Br)=[CH:93][C:92]=1[CH2:108][OH:109])[C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1>C(=O)([O-])O.[Na+].ClCCl>[NH3:7].[CH2:83]([O:90][C:91]1[CH:96]=[CH:95][C:94]([C@@H:97]([O:100][Si:101]([C:104]([CH3:107])([CH3:106])[CH3:105])([CH3:103])[CH3:102])[CH2:98][NH:30][CH2:29][CH2:28][C:25]2[CH:24]=[CH:23][C:22]([O:21][CH2:20][CH2:19][CH2:18][CH2:17][C:14]3[CH:15]=[CH:16][C:11]([OH:10])=[C:12]([C@@H:31]([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[CH2:32][CH2:33][N:34]([CH:35]([CH3:36])[CH3:37])[CH:38]([CH3:40])[CH3:39])[CH:13]=3)=[CH:27][CH:26]=2)=[CH:93][C:92]=1[CH2:108][OH:109])[C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1

Komponenten

6

Edukt 2

HCID 12988834[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanolHCID 1317277264-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol tert-butyl {2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}carbamate bis hydrochloride salt

Produkt 2

HCID 222AmmoniaHCID 579331564-{4-[4-(2-{[(2R)-2-[4-(benzyloxy)-3-(hydroxymethyl)phenyl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl]amino}ethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel2×

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

4-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol tert-butyl{2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}carbamate bis hydrochloride salt (Preparation 13, 1.30 g, 2.26 mmol), was dissolved in a mixture of saturated aqueous sodium hydrogen carbonate and dichloromethane. The organic layer was separated, dried (magnesium sulphate) and the solvent removed in vacuo The residue was dissolved in acetonitrile (10 ml) and {2-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanol (Prepared according to WO2004/032921, 1.02 mg, 2.26 mmol), sodium hydrogen carbonate (570 mg, 6.78 mmol) were added, and heated to 85° C. and stirred overnight. After cooling the solvent was removed in vacuo and the residue was dissolved in dichloromethane (30 ml) and washed with water (2×20 ml) then brine (20 ml), 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 (95/5/1 to 90/10/1 by volume) to furnish the title compound as a gum, 388 mg.

Aufarbeitung

  1. customThe organic layer was separated
  2. dry with materialdried (magnesium sulphate)
  3. customthe solvent removed in vacuo The residue
  4. dissolutionwas dissolved in acetonitrile (10 ml)
  5. temperatureAfter cooling the solvent
  6. customwas removed in vacuo
  7. dissolutionthe residue was dissolved in dichloromethane (30 ml)
  8. washwashed with water (2×20 ml)
  9. dry with materialbrine (20 ml), dried (magnesium sulphate)
  10. customthe solvent removed in vacuo
  11. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-0964138489f645d0a49a6f165cd09d5f
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07612084B2

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