Citric Acid → N,N-Diethyl-2-hydroxy-2-phenylacetamide

HRID 1186383Notes

Reaction equation

HRID 1186383 reaction equation
[OH:1][CH:2]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]([OH:5])=O.C[Si](Cl)(C)C.C(Cl)(=O)C(Cl)=O.[CH2:23]([NH:25][CH2:26][CH3:27])[CH3:24].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.CN(C1C=CN=CC=1)C.C(OCC)(=O)C.CO.N1C=CC=CC=1.CN(C)C=O>[CH2:23]([N:25]([CH2:26][CH3:27])[C:3](=[O:5])[CH:2]([OH:1])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH3:24]

Participants

12

Reactant 5

HCID 311Citric AcidHCID 1292Mandelic AcidHCID 6397ChlorotrimethylsilaneHCID 8021DiethylamineHCID 65578Oxalyl chloride

Product 1

HCID 121583N,N-Diethyl-2-hydroxy-2-phenylacetamideYield 89%

Reagents, catalysts & solvents 6

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 1049PyridineSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-Hydroxy-2-phenylacetic acid (500 mg, 3.29 mmol) was dissolved in dichloromethane (7.5 mL). To this, pyridine (0.532 mL, 6.58 mmol), DMAP (40 mg, 0.33 mmol) and trimethylsilyl chloride (0.835 mL, 6.58 mmol) were added at room temperature and the mixture was stirred for 7.8 hours. After the reaction mixture was cooled to 0° C., N,N-dimethylformamide (0.050 mL) and oxalyl chloride (0.301 mL, 3.45 mmol) were added thereto, and the mixture was stirred at a temperature of 0° C. to room temperature for 1 hour. After the reaction mixture was cooled to 0° C. again, a pyridine solution (0.878 mL) of diethylamine (0.374 mL, 3.62 mmol) was added thereto, and the mixture was stirred at a temperature of 0° C. to room temperature for 2 hours. Then, a methanol solution (5 mL) of citric acid (695 mg, 3.62 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 12 hours. After addition of ethyl acetate, the reaction mixture was filtered. One mol/L hydrochloric acid was added to the filtrate, and extraction with ethyl acetate was performed, followed by washing with saturated sodium carbonate and brine and drying over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, and thereby N,N-diethyl-2-hydroxy-2-phenylacetamide (Compound ED) (606 mg, yield: 89%) was obtained.

Workup

  1. stirringthe mixture was stirred at a temperature of 0° C. to room temperature for 1 hour
  2. temperatureAfter the reaction mixture was cooled to 0° C. again
  3. stirringthe mixture was stirred at a temperature of 0° C. to room temperature for 2 hours
  4. stirringthe mixture was stirred at room temperature for 12 hours
  5. filtrationthe reaction mixture was filtered
  6. additionOne mol/L hydrochloric acid was added to the filtrate, and extraction with ethyl acetate
  7. washby washing with saturated sodium carbonate and brine
  8. dry with materialdrying over anhydrous sodium sulfate
  9. customThe solvent was evaporated off under reduced pressure

Sources & evidence

ORD record
ord-8e84715118eb422197f1895e988df6d3
Source dataset
uspto-grants-2014_03
Patent number
US08673908B2

Reaction notes

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