Chloroacetyl chloride → HCID 10594703, compound

HRID 342130Notes

Reaction equation

HRID 342130 reaction equation
[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[NH:9][CH2:10][C@@H:11]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][CH2:13][CH2:14][CH3:15].C(=O)(O)[O-].[Na+].Cl[CH2:30][C:31](Cl)=[O:32].[H-].[Na+].[H][H]>C(OCC)(=O)C>[C:20]([O:19][C:17]([N:16]1[C@@H:11]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:10][N:9]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([CH3:8])[C:2]=2[CH3:1])[C:31](=[O:32])[CH2:30]1)=[O:18])([CH3:22])([CH3:21])[CH3:23]

Participants

7

Reactant 5

HCID 6577Chloroacetyl chlorideHCID 24758Sodium hydride2×HCID 516892Sodium BicarbonateHCID 10615682Carbamic acid, [(1S)-1-[[(2,3-dimethylphenyl)amino]methyl]pentyl]-, 1,1-dimethylethyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 10594703HCID 10594703, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of the product from Step C (8.50 g, 26.5 mmol) in ethyl acetate (250 mL) was vigorously stirred at 0° C. with saturated sodium bicarbonate (150 mL). Chloroacetyl chloride (2.33 mL, 29.1 mmol) was added, and the reaction stirred at ) 0° C. for 1 h. The layers were separated, and the ethyl acetate phase was washed with saturated brine, and dried over magnesium sulfate. The crude product was dissolved in DMF (300 mL) and cooled to 0° C. under nitrogen. Sodium hydride (1.79 g, 60% dispersion in oil, 44.9 mmol) was added portionwise to maintain moderate hydrogen evolution. After 30 min, an additional amount of sodium hydride was added (0.8 g). The reaction was stirred another 30 min, then quenched with saturated ammonium chloride. The DMF was distilled in vacuo, and the residue partitioned between ethyl acetate and water. The organic phase was washed with water, saturated brine, and dried over magnesium sulfate. The crude product was chromatographed on silica gel with 20-30% ethyl acetate in hexane to obtain the title compound.

Workup

  1. customThe layers were separated
  2. washthe ethyl acetate phase was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. dissolutionThe crude product was dissolved in DMF (300 mL)
  5. temperaturecooled to 0° C. under nitrogen
  6. waitAfter 30 min
  7. stirringThe reaction was stirred another 30 min
  8. customquenched with saturated ammonium chloride
  9. distillationThe DMF was distilled in vacuo
  10. customthe residue partitioned between ethyl acetate and water
  11. washThe organic phase was washed with water, saturated brine
  12. dry with materialdried over magnesium sulfate
  13. customThe crude product was chromatographed on silica gel with 20-30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-0709b95329f6419fbebad04fa45a6aa1
Source dataset
uspto-grants-1999_01
Patent number
US05856326

Reaction notes

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