Triethylamine → HCID 68773553, compound

HRID 1628574Notes

Reaction equation

HRID 1628574 reaction equation
[NH2:1][C:2]1[C:3]([NH:13][CH2:14][CH2:15][CH2:16][OH:17])=[C:4]([CH:9]=[CH:10][C:11]=1[Cl:12])[C:5]([O:7][CH3:8])=[O:6].C(N(CC)CC)C.C([O:28][CH:29]([C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=1[Cl:40])[C:30](Cl)=O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(OCC)(=O)C>[Cl:12][C:11]1[C:2]2[N:1]=[C:30]([CH:29]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=3[Cl:40])[OH:28])[N:13]([CH2:14][CH2:15][CH2:16][OH:17])[C:3]=2[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 68739849Methyl 3-amino-4-chloro-2-((3-hydroxypropyl)amino]benzoateHCID 86632918HCID 86632918, compound

Product 1

HCID 68773553HCID 68773553, compoundYield 41.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

To a stirred solution of methyl 3-amino-4-chloro-2-[(3-hydroxypropyl)amino]benzoate (1.01 g, 3.90 mmol) and triethylamine (1.20 mL, 8.58 mmol) in tetrahydrofuran (20 mL) was added a solution of 2-chloro-1-(2,4-dichlorophenyl)-2-oxoethyl acetate (2.20 g, 7.80 mmol) in tetrahydrofuran (10 mL) at 0° C. After 30 min, the reaction mixture was diluted with ethyl acetate, washed with brine, dried over sodium sulfate, filtrated, and concentrated in vacuo. The residue was dissolved in acetic acid (20 mL), and the mixture was stirred for 1 h at 80° C. The reaction mixture was concentrated in vacuo, diluted with ethyl acetate, washed with aqueous sodium hydrogen carbonate and brine, dried over sodium sulfate, filtrated, and concentrated in vacuo. The residue was dissolved in methanol (20 mL) and potassium carbonate (539 mg, 3.90 mmol) was added at room temperature. After 30 min, the reaction mixture was diluted with ethyl acetate, washed with brine, dried over sodium sulfate, filtrated, and concentrated in vacuo. The residue was purified by column chromatography on NH-silica gel eluting with a 0-10% methanol/ethyl acetate gradient mixture to afford the desired product as pale yellow solid (745 mg, 1.61 mmol, 41%).

Workup

  1. washwashed with brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltrated
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in acetic acid (20 mL)
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. additiondiluted with ethyl acetate
  8. washwashed with aqueous sodium hydrogen carbonate and brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltrated
  11. concentrationconcentrated in vacuo
  12. dissolutionThe residue was dissolved in methanol (20 mL)
  13. waitAfter 30 min
  14. washwashed with brine
  15. dry with materialdried over sodium sulfate
  16. filtrationfiltrated
  17. concentrationconcentrated in vacuo
  18. customThe residue was purified by column chromatography on NH-silica gel eluting with a 0-10% methanol/ethyl acetate gradient mixture

Sources & evidence

ORD record
ord-aa7aacdd55474500a6473ff6c134952f
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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