Ethanol → HCID 11413874, compound

HRID 1241520Notes

Reaction equation

HRID 1241520 reaction equation
O[C:2]1([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=2)[CH2:5][CH:4]([CH2:6][N:7]2[CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:3]1.CCO.CS(O)(=O)=O.[OH-].[Na+]>CO.[Pd]>[N:7]1([CH2:6][CH:4]2[CH2:5][CH:2]([C:12]3[CH:13]=[CH:14][C:15]([CH2:16][NH2:17])=[CH:18][CH:19]=3)[CH2:3]2)[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

7

Reactant 4

HCID 702EthanolHCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 11161180HCID 11161180, compound

Product 1

HCID 11413874HCID 11413874, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Conditions

Temperature
50 °C

Procedure

To a stirring soluiont of Example 213 (4-(1-Hydroxy-3-pyrrolidin-1-ylmethyl-cyclobutyl)-benzonitrile) (500 mg, 1.9 mmol) in 20 mL of each MeOH and EtOH was added methanesulfonic acid (1.3 mL, 19.5 mmol), followed by 125 mg of 10% palladium/carbon. The reaction vessel was purged several times with N2 and then pressurized with 45 psi H2. After 1 h the reaction mixture was purged with N2 filtered through a plug of Celite and concentrated under reduced pressure. This mixture was re-dissolved in EtOH (20 mL) then 10% Pd/C (125 mg) was added. As before the reaction vessel was purged several times with N2, pressurized with 45 psi H2 and then heated to 50° C. After 2 hours the reaction mixture was purged with N2, filtered through a plug of Celite, and concentrated under reduced pressure to yield viscous oil. This oil was taken up in MeOH and solid NaOH (780 mg, 19.5 mmol.) was added. This mixture was stirred overnight. The solid were then filtered off and the filtrate was concentrated. The HCl salt was made by the first dissolving the residual compound in EtOAc and then a solution of HCl (2N in EteO) was added. The solids was collected and dried under reduced pressure. Purification of this material was accomplished by dry pack method flash column chromatography using a 40 g ISCO column, eluting with a gradient of 10%–40% MeOH/CH2Cl2 with 0.2% NH4OH. The product containing fractions were collected and concentrated to give the title compound (350 mg, 74% yield) as a colorless solid. The HCl salt of the title compound was made treating the title compound in EtOAc with a solution of HCl (2N in Et2O).

Workup

  1. customThe reaction vessel was purged several times with N2
  2. customAfter 1 h the reaction mixture was purged with N2
  3. filtrationfiltered through a plug of Celite
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThis mixture was re-dissolved in EtOH (20 mL)
  6. addition10% Pd/C (125 mg) was added
  7. customAs before the reaction vessel was purged several times with N2
  8. customAfter 2 hours the reaction mixture was purged with N2
  9. filtrationfiltered through a plug of Celite
  10. concentrationconcentrated under reduced pressure
  11. customto yield viscous oil
  12. filtrationThe solid were then filtered off
  13. concentrationthe filtrate was concentrated
  14. dissolutionfirst dissolving the residual compound in EtOAc
  15. additiona solution of HCl (2N in EteO) was added
  16. customThe solids was collected
  17. customdried under reduced pressure
  18. customPurification of this material
  19. customby dry pack method flash column chromatography
  20. washeluting with a gradient of 10%–40% MeOH/CH2Cl2 with 0.2% NH4OH
  21. additionThe product containing fractions
  22. customwere collected
  23. concentrationconcentrated

Sources & evidence

ORD record
ord-cb88918a8e324cad951484b2c1fe09b1
Source dataset
uspto-grants-2006_10
Patent number
US07115600B2

Reaction notes

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