Acetyl chloride → HCID 68432108, compound

HRID 2237766Notes

Reaction equation

HRID 2237766 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9](=O)[CH:10]=[C:11]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:12][CH2:13][CH2:14][O:15]C1CCCCO1.O.[NH2:30][NH2:31].[C:32](Cl)(=[O:34])[CH3:33].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>N1C=CC=CC=1>[C:32]([N:30]1[C:11]([CH2:12][CH2:13][CH2:14][OH:15])([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:10][C:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])=[N:31]1)(=[O:34])[CH3:33]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 24654Hydrazine hydrate (1:1)HCID 521998p-Toluenesulfonic acid monohydrateHCID 68432626HCID 68432626, compound

Product 1

HCID 68432108HCID 68432108, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 16.0 g (41.4 mmol) of 1-4 in 150 mL of pyridine was added 3.0 mL (62.1 mmol) of hydrazine hydrate, and the resulting mixture was heated at 90° C. for 45 min. After cooling to room temperature, the reaction was placed in an ice bath and 14.7 mL (207 mmol) of acetyl chloride was added dropwise. The bath was removed and the reaction was stirred overnight at room temperature before being dumped into a separatory funnel containing EtOAc and brine. The layers were separated, the organic was washed twice with 1M HCl, once with brine, dried over Na2SO4, and concentrated by rotary evaporation. The residue was twice resuspended in toluene and concentrated to azeotrope off any remaining pyridine. The residue was dissolved in 200 mL of MeOH and 8.0 g (42 mmol) of p-toluenesulfonic acid monohydrate was added. After stirring for 2 h at room temperature, most of the solvent was removed by rotary evaporation and the residue partitioned between saturated aqueous NaHCO3 and EtOAc. After separating the layers, the organic was washed again with bicarbonate, then brine, dried over Na2SO4, and concentrated by rotary evaporation. The residue was triturated with Et2O and the solid material was collected by filtration to provide racemic 1-5 as a white solid. Data for racemic 1-5: 1HNMR (500 MHz, CDCl3) δ 7.7 (m, 1H), 7.4-7.0 (m, 7H), 3.8-3.65 (m, 2H), 3.6 (m, 1H), 3.5 (m, 1H), 2.9 (m, 1H), 2.4 (s, 3H), 2.3 (m, 1H), 1.7-1.5 (m, 2H) ppm. HRMS (ES) calc'd M+H for C20H20F2N2O3: 359.1566. Found: 359.1557

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction was placed in an ice bath
  3. customThe bath was removed
  4. custombefore being dumped into a separatory funnel
  5. additioncontaining EtOAc and brine
  6. customThe layers were separated
  7. washthe organic was washed twice with 1M HCl, once with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated by rotary evaporation
  10. concentrationconcentrated
  11. dissolutionThe residue was dissolved in 200 mL of MeOH
  12. stirringAfter stirring for 2 h at room temperature, most of the solvent
  13. customwas removed by rotary evaporation
  14. customthe residue partitioned between saturated aqueous NaHCO3 and EtOAc
  15. customAfter separating the layers
  16. washthe organic was washed again with bicarbonate
  17. dry with materialbrine, dried over Na2SO4
  18. concentrationconcentrated by rotary evaporation
  19. customThe residue was triturated with Et2O
  20. filtrationthe solid material was collected by filtration

Sources & evidence

ORD record
ord-adc0a9b9e1ec416c825e4e11ae42efbd
Source dataset
uspto-grants-2010_05
Patent number
US07718687B2

Reaction notes

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