Hydrochloric Acid → 2-(4-Methoxyphenoxy)-1-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)ethanone

HRID 1487740Notes

Reaction equation

HRID 1487740 reaction equation
Cl.O1CCOCC1.OC(C(F)(F)F)=O.[CH3:15][O:16][C:17]1[CH:47]=[CH:46][C:20]([O:21][CH2:22][C:23]([N:25]2[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH:26]2[CH2:38][O:39][C:40]2[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=2)=[O:24])=[CH:19][CH:18]=1>>[CH3:15][O:16][C:17]1[CH:18]=[CH:19][C:20]([O:21][CH2:22][C:23]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH:26]2[CH2:38][O:39][C:40]2[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=2)=[O:24])=[CH:46][CH:47]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 131728857HCID 131728857, compound

Product 1

HCID 596715422-(4-Methoxyphenoxy)-1-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)ethanoneYield 19%

Procedure

4 M HCl in 1,4-dioxane (6 mL, 24 mmol) was added to tert-butyl 4-(2-(4-methoxyphenoxy)acetyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate TFA salt (182 mg, ≦0.305 mmol). After 12 h, the reaction mixture was concentrated under reduced pressure and purified by HPLC (5 to 50% MeCN/0.1% TFA in H2O/0.1% TFA gradient). The desired chromatography fractions were brought to pH ˜12 with 1 N NaOH and were extracted with EtOAc (3×10 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure, yielding 20.9 mg (19%) of the desired product as a thick oil. LC-MS: RT=3.76 min, [M+H]+=358.1.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. custompurified by HPLC (5 to 50% MeCN/0.1% TFA in H2O/0.1% TFA gradient)
  3. extractionwere extracted with EtOAc (3×10 mL)
  4. dry with materialThe combined organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b3e16007a6d64ef4ad0e024eb8a88dd9
Source dataset
uspto-grants-2016_08
Patent number
US09428522B2

Reaction notes

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