Chloroacetyl chloride → HCID 69597420, compound

HRID 342137Notes

Reaction equation

HRID 342137 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:19][CH2:20][S:21][CH3:22])[CH2:10][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].Cl[CH2:29][C:30](Cl)=[O:31].C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@@H:9]([CH2:19][CH2:20][S:21][CH3:22])[CH2:10][N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=2)[C:30](=[O:31])[CH2:29]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 10796Cesium carbonate2×HCID 516892Sodium BicarbonateHCID 57295847HCID 57295847, compound

Product 1

HCID 69597420HCID 69597420, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of the product from Step H (22.0 g, 63.9 mmol) in ethyl acetate (150 mL) was vigorously stirred at 0° C. with saturated sodium bicarbonate (150 mL). Chloroacetyl chloride (5.6 mL, 70.2 mmol) was added dropwise, and the reaction stirred at 0° C. for 2 h. The layers were separated, and the ethyl acetate phase was washed with 10% citric acid and saturated brine, and dried over sodium sulfate. After concentration in vacuo, the resulting crude product (27.6 g) was dissolved in DMF (300 mL) and cooled to 0° C. under argon. Cesium carbonate (63.9 g, 196 mmol) was added, and the reaction was stirred for two days, allowing it to warm to room temperature. Another portion of cesium carbonate (10 g, 30 mmol) was added, and the reaction was stirred for 16 hours. The DMF was distilled in vacuo, and the residue partitioned between ethyl acetate and water. The organic phase was washed with saturated brine, and dried over sodium sulfate. The crude product was chromatographed on silica gel with 20-25% ethyl acetate in hexane to obtain the title compound.

Workup

  1. customThe layers were separated
  2. washthe ethyl acetate phase was washed with 10% citric acid and saturated brine
  3. dry with materialdried over sodium sulfate
  4. concentrationAfter concentration in vacuo
  5. dissolutionthe resulting crude product (27.6 g) was dissolved in DMF (300 mL)
  6. temperaturecooled to 0° C. under argon
  7. stirringthe reaction was stirred for two days
  8. temperatureto warm to room temperature
  9. stirringthe reaction was stirred for 16 hours
  10. distillationThe DMF was distilled in vacuo
  11. customthe residue partitioned between ethyl acetate and water
  12. washThe organic phase was washed with saturated brine
  13. dry with materialdried over sodium sulfate
  14. customThe crude product was chromatographed on silica gel with 20-25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-d9c66ebd81234699a09b17f9d94b8da3
Source dataset
uspto-grants-1999_01
Patent number
US05856326

Reaction notes

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