Potassium Hydroxide → Sofinicline

HRID 898732Notes

Reaction equation

HRID 898732 reaction equation
C1(S(O)(=O)=O)C=CC=CC=1.[Cl:11][C:12]1[CH:13]=[C:14]([N:19]2[CH2:25][C@@H:24]3[C@@H:21]([CH2:22][NH:23]3)[CH2:20]2)[CH:15]=[N:16][C:17]=1[Cl:18].[OH-].[K+]>C(Cl)Cl>[Cl:11][C:12]1[CH:13]=[C:14]([N:19]2[CH2:25][C@@H:24]3[C@@H:21]([CH2:22][NH:23]3)[CH2:20]2)[CH:15]=[N:16][C:17]=1[Cl:18]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 11682800Sofinicline Benzenesulfonate

Product 1

HCID 10131048Sofinicline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

(1S,5S)-3-(5,6-dichloropyridin-3-yl)-3,6-diazabicyclo[3.2.0]heptane benzenesulfonate (250 g) was suspended in methylene chloride (1000 mL). 20% aqueous potassium hydroxide (700 mL) was added and, after mixing and settling, the layers were separated. The organic layer was washed two more times with 700 mL 20% aqueous potassium hydroxide, followed by a 700 mL water wash. The combined organic layers were dried over sodium sulfate and then concentrated to an oil. The residue was dissolved in isopropyl acetate (1000 mL) and concentrated to a solid. The residue was then suspended in isopropyl acetate (1000 mL) and heated to 80° C. to dissolve everything. Insolubles were removed by filtration. The solution was cooled to room temperature, with rapid stirring. The resulting slurry was concentrated further by distillation of approximately 250 mL isopropyl acetate. After cooling in the refrigerator for 3 hours (˜5° C.), the product was isolated by filtration. The wetcake was washed with isopropyl acetate and then dried in a vacuum oven at 50° C. An off-white solid was obtained (109.6 g).

Workup

  1. additionafter mixing
  2. customthe layers were separated
  3. washThe organic layer was washed two more times with 700 mL 20% aqueous potassium hydroxide
  4. washwash
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated to an oil
  7. dissolutionThe residue was dissolved in isopropyl acetate (1000 mL)
  8. concentrationconcentrated to a solid
  9. dissolutionto dissolve everything
  10. customInsolubles were removed by filtration
  11. temperatureThe solution was cooled to room temperature, with rapid stirring
  12. concentrationThe resulting slurry was concentrated further by distillation of approximately 250 mL isopropyl acetate
  13. temperatureAfter cooling in the refrigerator for 3 hours (˜5° C.)
  14. customthe product was isolated by filtration
  15. washThe wetcake was washed with isopropyl acetate
  16. customdried in a vacuum oven at 50° C
  17. customAn off-white solid was obtained (109.6 g)

Sources & evidence

ORD record
ord-ae297301953e47f89cc3733372775611
Source dataset
uspto-grants-2008_04
Patent number
US07351833B2

Reaction notes

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