Triethylamine → (6-Trifluoromethyl-7-(2(-4-chlorophenoxy)ethoxy)-1,2,3,4-tetrahydro-2,3-dioxoquinoxalin-1-yl]methanephosphonic acid diethyl ester

HRID 368965Notes

Reaction equation

HRID 368965 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][NH:10][C:11]1[CH:16]=[C:15]([O:17][CH2:18][CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[C:14]([C:28]([F:31])([F:30])[F:29])=[CH:13][C:12]=1[NH2:32])(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].C(N(CC)CC)C.[Cl-].C([O:43][C:44](=O)[C:45](O)=[O:46])C.Cl.C([NH+](CC)CC)C>O1CCCC1>[CH2:6]([O:5][P:4]([CH2:9][N:10]1[C:11]2[C:12](=[CH:13][C:14]([C:28]([F:30])([F:31])[F:29])=[C:15]([O:17][CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[CH:16]=2)[NH:32][C:44](=[O:43])[C:45]1=[O:46])(=[O:8])[O:3][CH2:1][CH3:2])[CH3:7]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10994676N-[2-amino-4-trifluoromethyl-5-(2(-4-chlorophenoxy)ethoxy)phenyl]-aminomethanephosphonic acid diethyl esterHCID 21900368Triethylammonium hydrochlorideHCID 23618337Oxalic acid monoethylester chloride

Product 1

HCID 15818832(6-Trifluoromethyl-7-(2(-4-chlorophenoxy)ethoxy)-1,2,3,4-tetrahydro-2,3-dioxoquinoxalin-1-yl]methanephosphonic acid diethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2.5 g of N-[2-amino-4-trifluoromethyl-5-(2(-4-chlorophenoxy)ethoxy)phenyl]-aminomethanephosphonic acid diethyl ester is introduced in 60 ml of tetrahydrofuran with 733 mg of triethylamine and mixed drop by drop at room temperature with a solution of 719 mg (0.59 ml) of oxalic acid ethyl ester chloride in 15 ml of tetrahydrofuran. Then, it is stirred for 2 hours at room temperature. After triethylammonium hydrochloride is suctioned out, the filtrate is concentrated by evaporation. The residue is taken up in 25 ml of ethanol and 25 ml of 1N hydrochloric acid and heated for 2 hours to a bath temperature of 120° C. After the ethanol is distilled off, it is diluted with water to 50 ml, and extracted three times with 50 ml of ethyl acetate each. The ethyl acetate phase is washed with water, dried, filtered and concentrated by evaporation. The residue is chromatographed on silica gel with methylene chloride:ethanol=10:1. 810 mg of [(6-trifluoromethyl-7-(2(-4-chlorophenoxy)ethoxy)-1,2,3,4-tetrahydro-2,3-dioxoquinoxalin-1-yl]methanephosphonic acid diethyl ester is obtained.

Workup

  1. concentrationthe filtrate is concentrated by evaporation
  2. temperature25 ml of 1N hydrochloric acid and heated for 2 hours to a bath temperature of 120° C
  3. distillationAfter the ethanol is distilled off
  4. additionit is diluted with water to 50 ml
  5. extractionextracted three times with 50 ml of ethyl acetate each
  6. washThe ethyl acetate phase is washed with water
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated by evaporation
  10. customThe residue is chromatographed on silica gel with methylene chloride

Sources & evidence

ORD record
ord-e9fbf938b4964a42b7d5bbb5752a1333
Source dataset
uspto-grants-2000_10
Patent number
US06136805

Reaction notes

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