Phosphate → {5-[(1R)-2-[Bis(phenylmethyl)amino]-1-hydroxyethyl]-2-[({[2-(trimethylsilyl)ethyl]oxy}methyl)oxy]phenyl}formamide

HRID 494168Notes

Reaction equation

HRID 494168 reaction equation
[C:1]1([CH2:7][N:8]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:9][C@@H:10]([C:12]2[CH:13]=[CH:14][C:15]([OH:21])=[C:16]([NH:18][CH:19]=[O:20])[CH:17]=2)[OH:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH3:31][Si:32]([CH3:39])([CH3:38])[CH2:33][CH2:34][O:35][CH2:36]Cl.P([O-])([O-])([O-])=O>CN(C=O)C.O>[C:1]1([CH2:7][N:8]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:9][C@@H:10]([C:12]2[CH:13]=[CH:14][C:15]([O:21][CH2:36][O:35][CH2:34][CH2:33][Si:32]([CH3:39])([CH3:38])[CH3:31])=[C:16]([NH:18][CH:19]=[O:20])[CH:17]=2)[OH:11])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 1061PhosphateHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 86606167(5-{(1R)-2-[Bis(phenylmethyl)amino]-1-hydroxyethyl}-2-hydroxyphenyl)formamide

Product 1

HCID 86606168{5-[(1R)-2-[Bis(phenylmethyl)amino]-1-hydroxyethyl]-2-[({[2-(trimethylsilyl)ethyl]oxy}methyl)oxy]phenyl}formamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of (5-{(1R)2-[bis(phenylmethyl)amino]-1-hydroxyethyl}-2-hydroxyphenyl)formamide (354 mg) in DMF (10 ml) under nitrogen was treated with sodium hydride (60% dispersion in mineral oil, 38 mg) and the mixture stirred at 20° for 10 min. 2-(Trimethylsilyl)ethoxymethyl chloride (0.17 ml) was added and the mixture was stirred at 20° for 3 h. Phosphate buffer solution (pH 6.5) and water were added and the mixture was extracted with EtOAc. The extract was washed with water and dried (Na2SO4). Solvent evaporation in vacuo gave a residue which was purified on a silica SPE bond elut cartridge (20 g) using a gradient of 0% to 2% MeOH in DCM (Gradmaster™). The appropriate fractions were evaporated in vacuo to give the title compound (286 mg). LCMS RT=3.08 min.

Workup

  1. stirringthe mixture was stirred at 20° for 3 h
  2. extractionthe mixture was extracted with EtOAc
  3. washThe extract was washed with water
  4. dry with materialdried (Na2SO4)
  5. customSolvent evaporation in vacuo
  6. customgave a residue which
  7. customwas purified on a silica SPE bond elut cartridge (20 g)
  8. customThe appropriate fractions were evaporated in vacuo

Sources & evidence

ORD record
ord-16021c0083924dffbedc654d9cb21ea8
Source dataset
uspto-grants-2009_05
Patent number
US07538127B2

Reaction notes

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