Dichloroacetyl chloride → diethyl 2-(2,2-dichloro-N-(3-(3-(2,6-dichlorophenyl)isoxazol-5-yl)phenyl)acetamido)ethylphosphonate

HRID 1782177Notes

Reaction equation

HRID 1782177 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[CH:13]=[C:12]([C:14]2[CH:15]=[C:16]([NH:20][CH2:21][CH2:22][P:23](=[O:30])([O:27][CH2:28][CH3:29])[O:24][CH2:25][CH3:26])[CH:17]=[CH:18][CH:19]=2)[O:11][N:10]=1.C(N(CC)CC)C.[Cl:38][CH:39]([Cl:43])[C:40](Cl)=[O:41]>C(Cl)Cl>[Cl:38][CH:39]([Cl:43])[C:40]([N:20]([CH2:21][CH2:22][P:23](=[O:30])([O:27][CH2:28][CH3:29])[O:24][CH2:25][CH3:26])[C:16]1[CH:17]=[CH:18][CH:19]=[C:14]([C:12]2[O:11][N:10]=[C:9]([C:3]3[C:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[CH:13]=2)[CH:15]=1)=[O:41]

Participants

5

Reactant 3

HCID 6593Dichloroacetyl chlorideHCID 8471TriethylamineHCID 57588335Diethyl 2-(3-(3-(2,6-dichlorophenyl)isoxazol-5-yl)phenylamino)ethylphosphonate

Product 1

HCID 57588307diethyl 2-(2,2-dichloro-N-(3-(3-(2,6-dichlorophenyl)isoxazol-5-yl)phenyl)acetamido)ethylphosphonate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Diethyl 2-(3-(3-(2,6-dichlorophenyl)isoxazol-5-yl)phenylamino)ethylphosphonate (660 mg, 1.4 mmol) was dissolved in anhydrous methylene chloride (10 mL) with triethylamine (0.28 mL, 1.7 mmol). The mixture was cooled in an ice-bath under nitrogen, then a solution of dichloroacetyl chloride (161 μL, 1.7 mmol) in anhydrous dichloromethane (0.5 mL) was added dropwise. After the addition was completed the ice-bath was removed and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with methylene chloride and then washed successively with water, 10% hydrochloric acid and saturated sodium bicarbonate solution. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 1:1 ethyl acetate:hexanes followed by 98:2 methylene chloride:methanol to give diethyl 2-(2,2-dichloro-N-(3-(3-(2,6-dichlorophenyl)isoxazol-5-yl)phenyl)acetamido)ethylphosphonate (Cpd. No. 1) as a white solid. 1H NMR (CDCl3): 7.94 (m, 1H), 7.79 (m, 1H), 7.64 (m, 1H), 7.46-7.40 (m, 2H), 7.43-7.36 (m, 2H), 6.72 (s, 1H), 5.85 (s, 1H), 4.08 (m, 6H), 2.13 (m, 2H), 1.33 ppm (m, 6H). MW=580 confirmed by LC-MS, tr=11.55 min (Method A) MH+=578-582.

Workup

  1. temperatureThe mixture was cooled in an ice-bath under nitrogen
  2. additionAfter the addition
  3. customwas removed
  4. additionThe reaction mixture was diluted with methylene chloride
  5. washwashed successively with water, 10% hydrochloric acid and saturated sodium bicarbonate solution
  6. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by flash column chromatography on silica gel
  10. washeluting with 1:1 ethyl acetate

Sources & evidence

ORD record
ord-a3c5b0ff62ce4d4fa218b3393f7980d0
Source dataset
uspto-grants-2009_03
Patent number
US07498353B2

Reaction notes

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