Hydrochloric Acid → 5-Methyl-2-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)benzo[d]oxazole hydrochloride

HRID 70207Notes

Reaction equation

HRID 70207 reaction equation
[ClH:1].O1CCOCC1.[CH3:8][C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([N:17]3[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH:18]3[CH2:30][O:31][C:32]3[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=3)=[N:14][C:13]=2[CH:38]=1>CO>[ClH:1].[CH3:8][C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH:18]3[CH2:30][O:31][C:32]3[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=3)=[N:14][C:13]=2[CH:38]=1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 312751,4-Dioxane2×HCID 59671587Tert-butyl 4-(5-methylbenzo[d]oxazol-2-yl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate

Product 1

HCID 667967055-Methyl-2-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)benzo[d]oxazole hydrochlorideYield 34%

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-(5-methylbenzo[d]oxazol-2-yl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate (212.9 mg, 0.502 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 fractions containing the desired product were brought to pH 12 with 1 N NaOH and were extracted with EtOAc (3×). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was dissolved in MeOH (1 mL) and 4 M HCl in 1,4-dioxane (1 equiv. HCl, 0.057 mL) was added. The mixture was concentrated under reduced pressure to give 60.8 mg (34%) of the desired product as the hydrochloride salt. LC-MS: RT=4.45 min, [M+H]+=325.1.

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. additionThe fractions containing the desired product
  4. extractionwere extracted with EtOAc (3×)
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe material was dissolved in MeOH (1 mL)
  9. concentrationThe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-f15fba993f6d427780bd7bd772a69536
Source dataset
uspto-grants-2014_09
Patent number
US08822472B2

Reaction notes

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