Acetyl chloride → HCID 11604245, compound

HRID 736457Notes

Reaction equation

HRID 736457 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[CH2:7][CH2:8]/[C:9](=[C:16]1\[CH2:17][O:18][C:19]2[C:24]([C:25]\1=O)=[CH:23][C:22]([F:27])=[CH:21][CH:20]=2)/[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.O.[NH2:29][NH2:30].[C:31](Cl)(=[O:33])[CH3:32]>N1C=CC=CC=1>[C:31]([N:29]1[C:9]([CH2:8][CH2:7][CH:2]2[O:1][CH2:6][CH2:5][CH2:4][O:3]2)([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:16]2[CH2:17][O:18][C:19]3[CH:20]=[CH:21][C:22]([F:27])=[CH:23][C:24]=3[C:25]2=[N:30]1)(=[O:33])[CH3:32]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 24654Hydrazine hydrate (1:1)HCID 57849018HCID 57849018, compound

Product 1

HCID 11604245HCID 11604245, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 225 mg (0.61 mmol) 5-3 in 10 mL of pyridine was added 45 μL (0.92 mmol) hydrazine hydrate and the reaction was heated for 1 h at 90° C. After cooling to room temperature, and then to 0° C., 220 μL (3.05 mmol) of acetyl chloride was added, the cooling bath was removed, and the reaction was stirred at room temperature overnight. The reaction was dumped into a separatory funnel containing EtOAc and brine, the layers were separated, the organic phase was washed again with brine, dried over Na2SO4, and concentrated. The residue was then resuspended twice in toluene and concentrated to azeotrope off any remaining pyridine, and then purified by silica gel chromatography with EtOAc/hexanes to provide 5-4 as a mixture of diastereomers. These were again purified on silica gel with a careful gradient of EtOAc/hexanes to provide the individual isomers, each as an off-white solid. Data for the first diastereomer of 5-4 to elute from silica: LC-MS: rt=2.67 min, m/z=425 (M+1). Data for the second diastereomer of 5-4 to elute from silica: LC-MS: rt=2.63 min, m/z=425 (M+1).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe cooling bath was removed
  3. customThe reaction was dumped into a separatory funnel
  4. additioncontaining EtOAc and brine
  5. customthe layers were separated
  6. washthe organic phase was washed again with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography with EtOAc/hexanes
  11. customto provide 5-4
  12. additionas a mixture of diastereomers
  13. customThese were again purified on silica gel with a careful gradient of EtOAc/hexanes
  14. customto provide the individual isomers
  15. washData for the first diastereomer of 5-4 to elute from silica
  16. customrt=2.67 min, m/z=425 (M+1)
  17. washData for the second diastereomer of 5-4 to elute from silica
  18. customrt=2.63 min, m/z=425 (M+1)

Sources & evidence

ORD record
ord-8b9bb8a096274de09458833648cebd38
Source dataset
uspto-grants-2009_09
Patent number
US07595337B2

Reaction notes

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