Phosphate → N-Cyclohexyl-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 219013Notes

Reaction equation

HRID 219013 reaction equation
C[Si](C)(C)[O-].[K+].[CH:7]1([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])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.P([O-])([O-])([O-])=O>C1COCC1>[CH:7]1([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])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1

Participants

5

Reactant 3

HCID 1061PhosphateHCID 23668039Potassium trimethylsilanolateHCID 66845105N-Cyclohexyl-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 66845388N-Cyclohexyl-N'-[3-({2-[(6-{[(2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl]amino}hexyl)oxy]ethoxy}methyl)phenyl]ureaYield 69.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Potassium trimethylsilanolate (0.177 g) was added to a solution of N-cyclohexyl-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 (0.207 g) in deoxygenated anhydrous THF (6 ml) whilst stirring under nitrogen. The reaction mixture was heated to 65° C. for 4.5 h, at which point the reaction mixture was cooled to room temperature. Phosphate buffer (25 ml, pH6.5) was added and the mixture left to stir for 10 min before extracting 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 (0.138 g). LCMS RT=2.87 min, ES+ve 598 (MH)+.

Workup

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

Sources & evidence

ORD record
ord-4d4b257b60f0462ca307ce4c0540d26a
Source dataset
uspto-grants-2012_06
Patent number
US08198483B2

Reaction notes

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