Sodium Hydroxide → Methyl-(4-{(2r)-2-[(2r)-2-(4-benzyloxy-3-hydroxymethyl-phenyl)-2-(tert-butyldimethylsilanyloxy)ethylamino]propyl}phenyl)acetate

HRID 916076Notes

Reaction equation

HRID 916076 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH2:14])[CH3:13])=[CH:7][CH:6]=1.[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][C:27]([C@@H:30]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH2:31]Br)=[CH:26][C:25]=1[CH2:41][OH:42])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(C(C)C)CC)(C)C.[OH-].[Na+]>CS(C)=O.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH:14][CH2:31][C@@H:30]([C:27]2[CH:28]=[CH:29][C:24]([O:23][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[C:25]([CH2:41][OH:42])[CH:26]=2)[O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH3:13])=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 12988834[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanolHCID 58959790Methyl-{4-[(2r)-2-amino-propyl]phenyl}acetate

Product 1

HCID 71168634Methyl-(4-{(2r)-2-[(2r)-2-(4-benzyloxy-3-hydroxymethyl-phenyl)-2-(tert-butyldimethylsilanyloxy)ethylamino]propyl}phenyl)acetateYield 50.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl-{4-[(2R)-2-amino-propyl]phenyl}acetate (Preparation 64) (7.00 g, 33.8 mmol), [2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanol (Preparation 39) (15.2 g, 33.8 mmol) and diisopropylethylamine (4.36 g, 33.8 mmol) were heated in dimethylsulfoxide (50 ml) at 90° C. under nitrogen for 16 hours. The mixture was cooled and diluted with ethyl acetate (250 ml) and basified with 1M aqueous sodium hydroxide. The aqueous was extracted with ethyl acetate (250 ml) and the combined organics washed with brine (3×200 ml) and dried (magnesium sulfate). The crude material was purified by chromatography (90:10 dichloromethane:methanol) to furnish an orange coloured oil (9.86 g).

Workup

  1. temperatureThe mixture was cooled
  2. extractionThe aqueous was extracted with ethyl acetate (250 ml)
  3. washthe combined organics washed with brine (3×200 ml)
  4. dry with materialdried (magnesium sulfate)
  5. customThe crude material was purified by chromatography (90:10 dichloromethane:methanol)

Sources & evidence

ORD record
ord-f91081b6cd8e48b587cfde224a8a2f22
Source dataset
uspto-grants-2007_09
Patent number
US07268147B2

Reaction notes

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