Lithium hydroxide, monohydrate → (3-{[6-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridine-3-carbonyl]-amino}-piperidin-1-yl)-acetic acid

HRID 1521006Notes

Reaction equation

HRID 1521006 reaction equation
C([O:3][C:4](=[O:35])[CH2:5][N:6]1[CH2:11][CH2:10][CH2:9][CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][C:18]([O:21][CH2:22][C:23]3[C:24]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[N:25][O:26][C:27]=3[CH3:28])=[CH:19][CH:20]=2)=[O:14])[CH2:7]1)C.O.[OH-].[Li+]>C1COCC1.O.CO.Cl>[CH3:28][C:27]1[O:26][N:25]=[C:24]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]=1[CH2:22][O:21][C:18]1[N:17]=[CH:16][C:15]([C:13]([NH:12][CH:8]2[CH2:9][CH2:10][CH2:11][N:6]([CH2:5][C:4]([OH:35])=[O:3])[CH2:7]2)=[O:14])=[CH:20][CH:19]=1

Participants

8

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68445346(3-{[6-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridine-3-carbonyl]-amino}-piperidin-1-yl)-acetic acid ethyl ester

Product 1

HCID 57520097(3-{[6-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridine-3-carbonyl]-amino}-piperidin-1-yl)-acetic acidYield 84.8%

Reagents, catalysts & solvents 5

HCID 313Hydrochloric AcidCatalystHCID 887MethanolCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3-{[6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridine-3-carbonyl]-amino}-piperidin-1-yl)-acetic acid ethyl ester (538 mg, 1.1 mmol) in THF (5 mL) was added a solution of lithium hydroxide monohydrate (94 mg, 2.2 mmol) in water (5 mL) and methanol (1 mL) added and the resulting mixture stirred at room temperature overnight. The mixture was acidified to pH 4 with HCl (25%, 3 drops) and methanol (2 drops) added. A gum began to form and the mixture was cooled at 0° C. for 1.5 h and then the aqueous layer decanted off. Trituration with diethylether and hexane afforded the title compound (420 mg, 83%) which was obtained as an off white solid. MS: m/e=449.0 [M−H]−.

Workup

  1. additionadded
  2. additionadded
  3. customto form
  4. temperaturethe mixture was cooled at 0° C. for 1.5 h
  5. customthe aqueous layer decanted off

Sources & evidence

ORD record
ord-f1f4aa2c384d40fb96afee213d187ba8
Source dataset
uspto-grants-2015_07
Patent number
US09073908B2

Reaction notes

Loading…