Triethylamine → Diethyl 2-(3-(3-(2,6-dichlorophenyl)isoxazol-5-yl)phenylamino)ethylphosphonate

HRID 1782176Notes

Reaction equation

HRID 1782176 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([Cl:12])[C:3]=1[C:4](Cl)=[N:5][OH:6].[C:13]([C:15]1[CH:16]=[C:17]([NH:21][CH2:22][CH2:23][P:24](=[O:31])([O:28][CH2:29][CH3:30])[O:25][CH2:26][CH3:27])[CH:18]=[CH:19][CH:20]=1)#[CH:14].C(N(CC)CC)C>O1CCCC1>[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([Cl:12])[C:3]=1[C:4]1[CH:14]=[C:13]([C:15]2[CH:16]=[C:17]([NH:21][CH2:22][CH2:23][P:24](=[O:31])([O:28][CH2:29][CH3:30])[O:25][CH2:26][CH3:27])[CH:18]=[CH:19][CH:20]=2)[O:6][N:5]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 28001642,6-DichlorobenzaldchloroximeHCID 57588428Diethyl 2-(3-ethynylphenylamino)ethylphosphonate

Product 1

HCID 57588335Diethyl 2-(3-(3-(2,6-dichlorophenyl)isoxazol-5-yl)phenylamino)ethylphosphonateYield 89.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,6-Dichloro-N-hydroxybenzimidoyl chloride (370 mg, 1.6 mmol) and diethyl 2-(3-ethynylphenylamino)ethylphosphonate (450 mg, 1.6 mmol) were dissolved in anhydrous tetrahydrofuran (40 mL) and triethylamine (0.30 mL, 1.6 mmol). The mixture was then heated at reflux for 5 h. The reaction was cooled to room temperature and the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed successively with water and brine. The ethyl acetate solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting solid was purified by flash column chromatography on silica gel, eluting with 98:2 methylene chloride:methanol to give diethyl 2-(3-(3-(2,6-dichlorophenyl)isoxazol-5-yl)phenylamino)ethylphosphonate (670 mg) as a pale yellow oil. 1H NMR (CDCl3): 7.30 (m, 2H), 7.21 (m, 1H), 7.15 (m, 1H), 7.05 (m, 1H), 7.00 (m, 1H), 6.59 (m, 1H), 6.48 (s, 1H), 4.03 (m, 4H), 3.40 (m, 2H), 2.00 (m, 2H), 1.24 ppm (m, 6H). MW=469 confirmed by LC-MS, tr=14.80 min (Method Y) MH+=467-472.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureat reflux for 5 h
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed successively with water and brine
  6. dry with materialThe ethyl acetate solution was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting solid was purified by flash column chromatography on silica gel
  10. washeluting with 98:2 methylene chloride

Sources & evidence

ORD record
ord-6f1d4e2fd773458f8602059d2230dd49
Source dataset
uspto-grants-2009_03
Patent number
US07498353B2

Reaction notes

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