Water → Ammonia

HRID 1433304Notes

Reaction equation

HRID 1433304 reaction equation
[Si]([O:8][C@H:9]([C:46]1[CH:51]=[CH:50][C:49]([OH:52])=[C:48]([CH2:53][OH:54])[CH:47]=1)[CH2:10][NH:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[C:25]([C@@H:30]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:31][CH2:32][N:33]([CH:37]([CH3:39])[CH3:38])[CH:34]([CH3:36])[CH3:35])[CH:24]=2)=[CH:16][CH:15]=1)(C(C)(C)C)(C)C.O.[F-].[NH4+].C(=O)([O-])O.[Na+]>CO.C(OCC)(=O)C>[NH3:11].[CH:37]([N:33]([CH:34]([CH3:36])[CH3:35])[CH2:32][CH2:31][C@@H:30]([C:25]1[CH:24]=[C:23]([CH2:22][CH2:21][O:20][C:17]2[CH:18]=[CH:19][C:14]([CH2:13][CH2:12][NH:11][CH2:10][C@H:9]([OH:8])[C:46]3[CH:51]=[CH:50][C:49]([OH:52])=[C:48]([CH2:53][OH:54])[CH:47]=3)=[CH:15][CH:16]=2)[CH:28]=[CH:27][C:26]=1[OH:29])[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)([CH3:38])[CH3:39]

Participants

8

Reactant 4

HCID 962WaterHCID 25516Ammonium fluorideHCID 516892Sodium BicarbonateHCID 579332144-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({2-[4-(2-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}ethoxy)phenyl]ethyl}amino)ethyl]-2-(hydroxymethyl)phenol

Product 2

HCID 222AmmoniaHCID 248764892-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-(2-{4-[2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)ethyl]phenoxy}ethyl)phenol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

4-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({2-[4-(2-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}ethoxy)phenyl]ethyl}amino)ethyl]-2-(hydroxymethyl)phenol (Preparation 49, 235 mg, 0.30 mmol) was dissolved in methanol (2.9 ml) and water (1.4 ml) and ammonium fluoride (112 mg, 3.0 mmol) was added. The reaction was heated to 40° C. and stirred overnight, cooled to room temperature and then saturated aqueous sodium hydrogen carbonate (20 ml) and ethyl acetate (20 ml) were added. The aqueous was separated and extracted 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 (80/20/1.0 by volume) to furnish the title compound as a glass, 55 mg.

Workup

  1. temperaturecooled to room temperature
  2. customThe aqueous was separated
  3. extractionextracted with ethyl acetate
  4. dry with materialthe combined organics dried (magnesium sulphate)
  5. customthe solvent removed in vacuo
  6. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-5a84747bba68437d88217e24cc45b381
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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