Trifluoroacetic acid → Ethyl 2-(3,4-dichloroanilino)acetate

HRID 2354313Notes

Reaction equation

HRID 2354313 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[Cl:9])[NH2:5].Br[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13].C(N(C(C)C)CC)(C)C.FC(F)(F)C(O)=O.C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.O.CC#N.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:6]=[CH:7][C:8]=1[Cl:9]

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 72573,4-DichloroanilineHCID 7748Ethyl bromoacetateHCID 81531DiisopropylethylamineHCID 516892Sodium Bicarbonate

Product 1

HCID 2727804Ethyl 2-(3,4-dichloroanilino)acetateYield 97%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

3,4-Dichloroaniline (100 g, 0.617 mol), ethyl bromoacetate (68.4 mL, 0.617 mol), and diisopropylethylamine (129.0 mL, 0.740 mol) were combined in 300 mL of dry NMP and stirred at room temperature for 18 h. HPLC (Eclipse XDB-C18, 4.6×250 mm, 5 micron, 1-99% CH3CN/H2O with 0.1% trifluoroacetic acid) after 18 h at room temperature showed that most of the starting material (Rt=5.2 min) was consumed and that a new peak had formed (Rt=7.9 min). The reaction was heated to 90° C. for 1 h, at which point HPLC indicated that conversion was complete. The reaction was allowed to cool to room temperature and then poured onto 2.5 L of ice, 1.5 L of water, and 240 g of NaHCO3. A tan precipitate formed immediately, the suspension was stirred vigorously for 10 minutes and then filtered through a fritted glass funnel. The tan solid was air-dried for 20 h in a crystallizing dish and then transferred to a 1 L flask and dried by rotary evaporation to remove the bulk of the remaining water. The tan solid was further dried under high vacuum to give 148 g (97%) of the title compound. LC/MS (APCI) m/e 248 [M+H]+.

Workup

  1. customthat most of the starting material (Rt=5.2 min) was consumed and that a new peak
  2. customhad formed (Rt=7.9 min)
  3. temperatureThe reaction was heated to 90° C. for 1 h, at which point HPLC
  4. temperatureto cool to room temperature
  5. customA tan precipitate formed immediately
  6. stirringthe suspension was stirred vigorously for 10 minutes
  7. filtrationfiltered through a fritted glass funnel
  8. customThe tan solid was air-dried for 20 h in a crystallizing dish
  9. customtransferred to a 1 L flask
  10. customdried by rotary evaporation
  11. customto remove the bulk of the remaining water
  12. customThe tan solid was further dried under high vacuum

Sources & evidence

ORD record
ord-d7d96c53b30d423eb1db0dff444874bd
Source dataset
uspto-grants-2010_07
Patent number
US07749998B2

Reaction notes

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