Thionyl Chloride → {[5-Bromo-2-({3-Chloro-4-[(2-methylphenyl)carbonyl]phenyl}amino)benzyl]oxy}ethyl (diethoxyphosphoryl)acetate

HRID 1797309Notes

Reaction equation

HRID 1797309 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]([OH:12])=[O:11])([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].S(Cl)(Cl)=O.[Br:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[CH3:39])=[O:32])=[C:27]([Cl:40])[CH:26]=2)=[C:20]([CH2:41][O:42][CH2:43][CH2:44]O)[CH:19]=1>C1(C)C=CC=CC=1.C1COCC1.CCOC(C)=O.C([O-])(O)=O.[Na+]>[CH2:7]([O:6][P:4]([CH2:9][C:10]([O:12][CH2:44][CH2:43][O:42][CH2:41][C:20]1[CH:19]=[C:18]([Br:17])[CH:23]=[CH:22][C:21]=1[NH:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[CH3:39])=[O:32])=[C:27]([Cl:40])[CH:26]=1)=[O:11])([O:3][CH2:1][CH3:2])=[O:5])[CH3:8]

Participants

8

Reactant 3

HCID 24386Thionyl ChlorideHCID 36704(Diethoxyphosphinyl)acetic acidHCID 10227340[4-({4-Bromo-2-[(2-hydroxyethoxy)methyl]phenyl}amino)-2-chlorophenyl](2-methylphenyl)methanone

Product 1

HCID 86588591{[5-Bromo-2-({3-Chloro-4-[(2-methylphenyl)carbonyl]phenyl}amino)benzyl]oxy}ethyl (diethoxyphosphoryl)acetate

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

The reactions were performed under an argon atmosphere using oven dried glass ware. Diethylphosphonoacetic acid (0.053 mL, 0.33 mmol) was dissolved in dry toluene (2 mL) and thionylchloride (0.065 mL, 0.9 mmol) was added. The reaction mixture was refluxed for 2 h and then concentrated in vacuo. Compound 158 (0.14 g, 0.3 mmol) was dissolved in dry THF (1.5 mL). 4-N,N-dimethylaminopyridine (0.073 g, 0.6 mmol) was added followed by addition of the above acid chloride dissolved in THF(1.5 mL). The reaction mixture was heated at reflux temperature for 20 h. The reaction mixture was diluted with EtOAc and aqueous NaHCO3, and the organic phase was washed with H2O and brine, and the combined water phases were extracted with EtOAc. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography using EtOAc/petroleum ether 2:1 as the eluent to afford the title compound as a slightly coloured oil.

Workup

  1. customdried glass ware
  2. temperatureThe reaction mixture was refluxed for 2 h
  3. concentrationconcentrated in vacuo
  4. temperatureThe reaction mixture was heated
  5. temperatureat reflux temperature for 20 h
  6. washthe organic phase was washed with H2O and brine
  7. extractionthe combined water phases were extracted with EtOAc
  8. dry with materialThe combined organic phases were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-364338989da74aa2bdd7fa87170e66cd
Source dataset
uspto-grants-2006_04
Patent number
US07034015B2

Reaction notes

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