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

HRID 1433292Notes

Reaction equation

HRID 1433292 reaction equation
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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent2×

Conditions

Temperature
85 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-0964138489f645d0a49a6f165cd09d5f
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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