Chloroacetyl chloride → HCID 66836087, compound

HRID 473591Notes

Reaction equation

HRID 473591 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([NH:12][CH2:13][CH2:14][NH:15][C:16]2[N:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN([CH2:27][CH3:28])CC.ClCC(Cl)=[O:32].[H-].[Na+]>C(Cl)Cl.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([N:12]2[CH2:28][CH2:27][N:15]([C:16]3[N:17]=[CH:18][CH:19]=[CH:20][N:21]=3)[CH2:14][C:13]2=[O:32])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 66823705HCID 66823705, compound

Product 1

HCID 66836087HCID 66836087, compoundYield 19.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of intermediate 2b (210 mg, 0.72 mmol) and Et3N (0.50 mL, 3.58 mmol) in CH2Cl2 (8 mL) at 0° C. was added chloroacetyl chloride (0.086 mL, 1.07 mmol). The reaction was slowly warmed up to room temperature in 3 h. It was quenched with aq. NaHCO3 and extracted with CH2Cl2. The organic solution was dried over Na2SO4 and concentrated. To a solution of the above crude product (150 mg, 0.41 mmol) in DMF (3 mL) at 0° C. was added NaH (60% in oil, 24 mg, 0.60 mmol). The reaction was slowly warmed up to room temperature in 3 h. It was quenched with H2O and extracted with EtOAc. The organic solution was washed with aq. NaCl, dried over Na2SO4 and concentrated. Purification by column chromatography (silica gel, 3% MeOH/CH2Cl2) gave intermediate 2c as white solid (47 mg).

Workup

  1. customIt was quenched with aq. NaHCO3
  2. extractionextracted with CH2Cl2
  3. dry with materialThe organic solution was dried over Na2SO4
  4. concentrationconcentrated
  5. temperatureThe reaction was slowly warmed up to room temperature in 3 h
  6. customIt was quenched with H2O
  7. extractionextracted with EtOAc
  8. washThe organic solution was washed with aq. NaCl
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customPurification by column chromatography (silica gel, 3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-49513705cce047508beb69790aa851fb
Source dataset
uspto-grants-2014_01
Patent number
US08637498B2

Reaction notes

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