Hydrochloric Acid → (2-Phenyloxazol-4-yl)(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)methanone dihydrochloride

HRID 70176Notes

Reaction equation

HRID 70176 reaction equation
[ClH:1].O1CCOCC1.OC(C(F)(F)F)=O.[C:15]1([C:21]2[O:22][CH:23]=[C:24]([C:26]([N:28]3[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH:29]3[CH2:41][O:42][C:43]3[CH:44]=[N:45][CH:46]=[CH:47][CH:48]=3)=[O:27])[N:25]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CO>[ClH:1].[ClH:1].[C:15]1([C:21]2[O:22][CH:23]=[C:24]([C:26]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH:29]3[CH2:41][O:42][C:43]3[CH:44]=[N:45][CH:46]=[CH:47][CH:48]=3)=[O:27])[N:25]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 131728862HCID 131728862, compound

Product 1

HCID 66797311(2-Phenyloxazol-4-yl)(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)methanone dihydrochlorideYield 67%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4 M HCl in 1,4-dioxane (6 mL, 24 mmol) was added to a solution of tert-butyl 4-(2-phenyloxazole-4-carbonyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate TFA salt (44.8 mg, 0.077 mmol) in MeOH (1 mL). After stirring overnight, 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 concentrated under reduced pressure, dissolved in MeOH (1 mL), and treated with 4 M HCl in 1,4-dioxane (6 mL). This was concentrated under reduced pressure, yielding 22.6 mg (67%) of the desired product as a white solid. LC-MS: RT=4.36 min, [M+H]+=365.0.

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. concentrationThe desired chromatography fractions were concentrated under reduced pressure
  4. dissolutiondissolved in MeOH (1 mL)
  5. additiontreated with 4 M HCl in 1,4-dioxane (6 mL)
  6. concentrationThis was concentrated under reduced pressure

Sources & evidence

ORD record
ord-7e25999010604926b0b75a9e21860a1f
Source dataset
uspto-grants-2014_09
Patent number
US08822472B2

Reaction notes

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