Hydrochloric Acid → HCID 178487566, compound

HRID 253230Notes

Reaction equation

HRID 253230 reaction equation
[H-].[Na+].[C:3]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)=[C:8]([O:27][CH3:28])[CH:7]=1)#[N:4].C(O[CH2:33][CH3:34])(=O)C.Cl.O1CCOCC1.[NH2:42][NH2:43]>C1COCC1.C(O)C>[NH2:4][C:3]1[NH:43][N:42]=[C:33]([CH3:34])[C:5]=1[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:16][CH2:15]2)=[C:8]([O:27][CH3:28])[CH:7]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 9321HydrazineHCID 24758Sodium hydrideHCID 312751,4-DioxaneHCID 66890484HCID 66890484, compound

Product 1

HCID 178487566HCID 178487566, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To NaH (60 wt. % dispersion in oil; 0.42 g, 10.5 mmol) suspended in THF (20 mL) was added 1,1-dimethylethyl 4-({[4-(cyanomethyl)-2-(methyloxy)phenyl]oxy}methyl)piperidine-1-carboxylate (1.73 g, 4.81 mmol) and then anhydrous ethyl acetate (0.559 mL, 5.73 mmol). The mixture was stirred at 60° C. for 15 h. The mixture was cooled to room temperature, was acidified with 4 N HCl in dioxane (2 mL, 8 mmol) and was concentrated in vacuo. The residue was partitioned between 1 N hydrochloric acid and ethyl acetate. The organic portion was washed with water, brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a red oil which was dissolved in ethanol (20 mL) and treated with hydrazine (0.185 mL, 5.84 mmol) at reflux for 1 h. The mixture was concentrated in vacuo and dried in vacuo to afford 1,1-dimethylethyl 4-({[4-(5-amino-3-methyl-1H-pyrazol-4-yl)-2-(methyloxy)phenyl]oxy}methyl)piperidine-1-carboxylate as a red foam (2.00 g, 4.81 mmol, 100% yield). MS (EI) for C22H32N4O4: 417 (MH+), 439 (MNa+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationwas concentrated in vacuo
  3. customThe residue was partitioned between 1 N hydrochloric acid and ethyl acetate
  4. washThe organic portion was washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a red oil which
  9. temperatureat reflux for 1 h
  10. concentrationThe mixture was concentrated in vacuo
  11. customdried in vacuo

Sources & evidence

ORD record
ord-c9cc1f59e2a747258ed7cd3f2a08ede0
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

Loading…