Phosphate → N-(1,1'-Biphenyl-4-yl)-N'-[3-({2-{(6-{[(2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl]amino}hexyl)oxy]ethoxy}methyl)phenyl]urea

HRID 901591Notes

Reaction equation

HRID 901591 reaction equation
C[Si](C)(C)[O-].[K+].[C:7]1([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH:12]=[CH:11][C:10]([NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][N:34]3[CH2:38][C@@H:37]([C:39]4[CH:50]=[CH:49][C:42]5[O:43][C:44]([CH3:48])([CH3:47])[O:45][CH2:46][C:41]=5[CH:40]=4)[O:36]C3=O)[CH:18]=2)=[O:15])=[CH:9][CH:8]=1.P([O-])([O-])([O-])=O>C1COCC1>[C:7]1([C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)[CH:12]=[CH:11][C:10]([NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][NH:34][CH2:38][C@@H:37]([C:39]3[CH:50]=[CH:49][C:42]4[O:43][C:44]([CH3:47])([CH3:48])[O:45][CH2:46][C:41]=4[CH:40]=3)[OH:36])[CH:18]=2)=[O:15])=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 1061PhosphateHCID 23668039Potassium trimethylsilanolateHCID 66845484N-(1,1'-Biphenyl-4-yl)-N'-(3-{[2-({6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexyl}oxy)ethoxy]-methyl}phenyl)urea

Product 1

HCID 66844972N-(1,1'-Biphenyl-4-yl)-N'-[3-({2-{(6-{[(2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl]amino}hexyl)oxy]ethoxy}methyl)phenyl]ureaYield 80.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Potassium trimethylsilanolate (0.090 g) was added to a solution of N-(1,1′-biphenyl-4-yl)-N′-(3-{[2-({6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexyl}oxy)ethoxy]methyl}phenyl)urea (0.119 g) in deoxygenated anhydrous THF (4 ml) whilst stirring under nitrogen. The reaction mixture was heated to 65° C. for 3 h, at which point the reaction mixture was cooled to room temperature. Phosphate buffer (25 ml, pH6.5) was added and the mixture extracted with EtOAc (3×25 ml). The combined organic layers were separated and dried over Na2SO4 before filtering. Solvent evaporation in vacuo gave a residue which was purified by Biotage. Elution with 150:8:1 dichloromethane:EtOH:ammonia followed by solvent evaporation in vacuo gave the title compound (0.092 g). LCMS RT=3.16 min, ES+ve 668 (MH)+.

Workup

  1. temperaturewas cooled to room temperature
  2. extractionthe mixture extracted with EtOAc (3×25 ml)
  3. customThe combined organic layers were separated
  4. dry with materialdried over Na2SO4
  5. filtrationbefore filtering
  6. customSolvent evaporation in vacuo
  7. customgave a residue which
  8. customwas purified by Biotage
  9. washElution with 150:8:1 dichloromethane
  10. customEtOH:ammonia followed by solvent evaporation in vacuo

Sources & evidence

ORD record
ord-133bd5df30fb43258e649cce1e099fd3
Source dataset
uspto-grants-2008_04
Patent number
US07361787B2

Reaction notes

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