Lithium Hydroxide → 4-((1-(Tert-butoxycarbonyl)piperidin-4-YL)oxy)-2-methoxybenzoic acid

HRID 1292339Notes

Reaction equation

HRID 1292339 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]([O: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)[CH:10]=[CH:9][C:4]=1[C:5]([O:7]C)=[O:6].[OH-].[Li+]>C1COCC1>[CH3:1][O:2][C:3]1[CH:12]=[C:11]([O: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)[CH:10]=[CH:9][C:4]=1[C:5]([OH:7])=[O:6]

Participants

4

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 10570851Tert-butyl 4-(3-methoxy-4-(methoxycarbonyl)phenoxy)piperidine-1-carboxylate

Product 1

HCID 105458744-((1-(Tert-butoxycarbonyl)piperidin-4-YL)oxy)-2-methoxybenzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-methoxy-4-(1-Boc-4-piperidyloxy)benzoate (4.5 g, 12.3 mmol) was dissolved in THF (200 ml) and treated with a solution of lithium hydroxide (17 ml of a 1.1M aqueous solution, 18.7 mmol) added over 5 min. The mixture was stirred at ambient temperature for 72 hours. An additional 4 ml of 1.1M lithium hydroxide was added and the mixture was heated at reflux for 13 hours, then stirred at ambient temperature for 18 hours. The reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and 1N hydrochloric acid. The organic layer was washed with brine, dried over sodium sulfate, filtered, and evaporated to dryness in vacuo to give 2-methoxy-4-(1-Boc-4-piperidyloxy)benzoic acid.

Workup

  1. additionadded over 5 min
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 13 hours
  4. stirringstirred at ambient temperature for 18 hours
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customthe residue partitioned between ethyl acetate and 1N hydrochloric acid
  7. washThe organic layer was washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated to dryness in vacuo

Sources & evidence

ORD record
ord-ae4d83abd34c4dbea731ccd7fb6cfd01
Source dataset
uspto-grants-1998_05
Patent number
US05756504

Reaction notes

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