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

HRID 2354369Notes

Reaction equation

HRID 2354369 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 di-isopropylethylamine (129.0 mL, 0.740 mol) were combined in 300 mL of dry N-methyl pyrrolidinone and stirred at room temperature for 18 hours. HPLC (Eclipse XDB-C18, 4.6×250 mm, 5 micron, 1-99% CH3CN/H2O with 0.1% trifluoroacetic acid) after 18 hours at room temperature showed that most of the starting material (Rt=5.2 min) was gone and that a new peak had formed (Rt=7.9 min). The reaction was heated to 90° C. to push it to completion, which was achieved after one hour at 90° C., as shown by HPLC. 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 and this suspension was stirred vigorously for 10 minutes and then filtered through a fritted glass funnel. The tan solid was air-dried for 20 hours 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 then dried under high vacuum to give 147.8 g (0.596 mol, 97%) of ethyl N-(3,4-dichlorophenyl)glycinate. LC/MS (APCI) m/e 248 [M+H]+.

Workup

  1. customhad formed (Rt=7.9 min)
  2. temperatureThe reaction was heated to 90° C.
  3. waitwas achieved after one hour at 90° C.
  4. temperatureto cool to room temperature
  5. customA tan precipitate formed immediately
  6. stirringthis suspension was stirred vigorously for 10 minutes
  7. filtrationfiltered through a fritted glass funnel
  8. customThe tan solid was air-dried for 20 hours 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 then dried under high vacuum

Sources & evidence

ORD record
ord-51ae9695a332411d8259c32fc272e657
Source dataset
uspto-grants-2010_07
Patent number
US07749998B2

Reaction notes

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