Lithium Hydroxide → HCID 44476487, compound

HRID 2192519Notes

Reaction equation

HRID 2192519 reaction equation
[NH:1]1[CH2:5][CH2:4][CH:3]([C:6]([OH:8])=[O:7])[CH2:2]1.[H-].[Na+].Cl[C:12]1[C:21]2[C:16](=[C:17]([C:22]3[N:26]=[C:25]([C:27]4[CH:32]=[CH:31][C:30]([O:33][CH:34]([CH3:36])[CH3:35])=[C:29]([Cl:37])[CH:28]=4)[O:24][N:23]=3)[CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][N:13]=1.[OH-].[Li+]>CS(C)=O.O1CCCC1.O.CO>[Cl:37][C:29]1[CH:28]=[C:27]([C:25]2[O:24][N:23]=[C:22]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:16]=3[CH:15]=[CH:14][N:13]=[C:12]4[N:1]3[CH2:5][CH2:4][CH:3]([C:6]([OH:8])=[O:7])[CH2:2]3)[N:26]=2)[CH:32]=[CH:31][C:30]=1[O:33][CH:34]([CH3:36])[CH3:35]

Participants

9

Reactant 4

HCID 3939Lithium HydroxideHCID 24758Sodium hydrideHCID 30346453-Pyrrolidinecarboxylic acidHCID 58149900HCID 58149900, compound

Product 1

HCID 44476487HCID 44476487, compoundYield 15%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-pyrrolidinecarboxylic acid (ABCR Product List; 36.0 mg, 0.312 mmol), and sodium hydride (60%; 9.99 mg, 0.250 mmol) in dimethyl sulfoxide (DMSO) (2 ml) were stirred at room temperature for 30 min. 1-Chloro-5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)isoquinoline (D7; 50 mg, 0.125 mmol) was added and the reaction mixture was left to stir at 120° C. under nitrogen for 3 hours. The cooled reaction mixture was loaded onto an SCX column. The column was flushed with methanol and then the desired product was eluted with 2M ammonia in methanol. The solvent was removed in vacuo from the appropriate fractions to give a yellow solid. Lithium hydroxide (2.99 mg, 0.125 mmol), methanol (2.00 ml), water (1 ml) and tetrahydrofuran (THF) (2.00 ml) were added and the mixture stirred at 80° C. for 1 hour. The solvent was removed in vacuo to give an orange solid which was triturated under ether and filtered. The solid was dissolved in water and then extracted with ether. The organic phase was passed through a hydrophobic frit and the solvent was removed in vacuo to give the title compound as a yellow solid (9 mg).

Workup

  1. waitthe reaction mixture was left
  2. stirringto stir at 120° C. under nitrogen for 3 hours
  3. customThe cooled reaction mixture
  4. customThe column was flushed with methanol
  5. washthe desired product was eluted with 2M ammonia in methanol
  6. customThe solvent was removed in vacuo from the appropriate fractions
  7. customto give a yellow solid
  8. stirringthe mixture stirred at 80° C. for 1 hour
  9. customThe solvent was removed in vacuo
  10. customto give an orange solid which
  11. customwas triturated under ether
  12. filtrationfiltered
  13. dissolutionThe solid was dissolved in water
  14. extractionextracted with ether
  15. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-fadb29b6ab57467a8de7e9646ec45e1c
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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